Methods in molecular biology (Clifton, N.J.)Amin Alvani, Negar Mottaghi-Dastjerd, Abozar Ghorbani, Ahmad Gholami, Zeinab Pazhoohesh
Conventional treatments often face challenges such as the limited ability to penetrate the blood-brain barrier (BBB). The Doxorubicin-loaded graphene oxide/magnetite (DOX/GO/Fe3O4) nanocomplex offers a promising platform due to GO's high surface area and pH-sensitive release, and Fe3O4's magnetic properties. This protocol describes the methodology for evaluating the cytotoxicity of free DOX versus the DOX/GO/Fe3O4 nanocomplex in the A-172 glioblastoma cell line, followed by advanced bioinformatics analysis to identify gene networks and indirect pathways that enhance the nanomaterial's biocompatibility. The methodology integrates the MTT assay, real-time PCR for apoptosis genes (Casp3, Bax, and Bcl-2), and advanced analysis, including protein-protein interaction (PPI) networking, clustering, and promoter motif analysis. The analysis indicated that miR-92a-2-5p is a potential therapeutic target for preventing myocardial damage and enhancing biocompatibility. The findings highlight key regulatory pathways that indirectly boost nanodrug biocompatibility through the modulation of secondary components like miRNAs and cellular stress mechanisms.
Mesenchymal stromal cells-derived extracellular vesicles (MSCs-EVs) represent innovative tools as a drug delivery system. Here, we described the standardized manufacturing process to prepare MSCs-EVs loaded with the chemotherapeutic drug Paclitaxel (PTX), starting from adipose tissue lipoaspirates of healthy donors.
Pakistan journal of pharmaceutical sciencesMuhammad Sajid Nawaz, Muhammad Zaman, Huma Hameed, Waqar Siddique, Ahmad Salawi, Yosif Almoshari, Jawaher Abdullah Alamoudi
BACKGROUND: Multiparticulate Drug Delivery (MDD) system are particularly considered as well suited systems for controlling oral preparations that have low risk of dose-dumping. OBJECTIVES: The current research work was aimed to prepare Fexofenadine HCl immediate release (IR) and Paracetamol sustained release (SR) pellets in a single dosage unit for the treatment of Allergic Rhinitis. Extrusion-spheronization was used to fabricate pellets. METHODS: The formulations were analyzed for several parameters, including micromeritic studies, Friability, Weight variation test, Swelling, X-Ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), in-vitro release and stability studies. RESULTS: The results showed that the formulated pellets have an excellent flowability (23.01° to 25.23°), bulk density falls in the range of 1.23 g cm -3 to 1.42 g cm -3 , tapped density ranges 1.43 g/cm 3 1.58 g/cm 3 , carr's compressibility index lie between 10.31 % to 15.17 %, Hausner's ratio ranges 1.11 to 1.18 which concluded pellets had good flow properties. Friability was less than 1%; the T6 formulation showed the maximum swelling of 99.28%. No interaction between excipient and drug was found. T6 showed a drug release of 99.08% in 24 hours. CONCLUSION: The research effectively demonstrated that preparing a single-unit dosage form of paracetamol and fexofenadine is a safe, simple and promising technique for SR of Paracetamol, thereby increasing patient compliance by reducing the dosage frequency.
Pakistan journal of pharmaceutical sciencesSana Hassan, Sadia Jafar Rana, Saman Zafar, Tahir Ali Chohan, Qalander Khan, Khizar Abbas, Muhammad Sohail Arshad
BACKGROUND: Chemotherapy-induced alopecia negatively impacts the mental health of cancer patients. Topical minoxidil, a widely recommended drug for hair regrowth, causes scalp irritation and contact dermatitis. Oral minoxidil causes multiple cardiovascular and neurological side effects. Cetirizine hydrochloride, an antihistamine with a better safety profile than minoxidil, may stimulate hair follicle activity by modulating prostaglandin levels. OBJECTIVES: The present study aimed to develop a cetirizine hydrochloride-loaded emulgel and evaluate its potential, in combination with microneedling, for the treatment of chemotherapy-induced alopecia. METHODS: Different emulgel formulations comprising cetirizine HCl, liquid paraffin, carbopol 940, propylene glycol, oleic acid, Tween 20, Span 20 and propylparaben were optimized using central composite design and response surface methodology. Physicochemical evaluation of the prepared emulgel included physical examination, determination of pH, viscosity, spreadability, drug content and stability. Interactions and compatibility among formulation constituents were assessed using In-silico analysis and Fourier transform infrared spectroscopy. In-vitro drug release, ex-vivo permeation and in-vivo hair growth studies were carried out to evaluate the performance efficiency of emulgel. RESULTS: The prepared emulgels exhibited acceptable physicochemical properties and remained stable for 3 months. Constituents were found to be compatible with each other. The optimized formulation F4 released >95% drug at pH 5.5 within 360 minutes. During an ex-vivo study, ~94% of the drug permeated across rat skin within 6 hours following application of emulgel on the microneedle-pretreated skin. In cyclophosphamide-induced alopecia in rats, application of emulgel to microneedle-pierced skin for 15 days promoted hair growth. CONCLUSION: The prepared cetirizine HCl-loaded emulgel and microneedle combination may be a promising approach to treating chemotherapy-induced alopecia.
AIMS: Although combining long-acting injectable antipsychotics (LAIs) with psychosocial treatments for schizophrenia is important, psychiatrists' attitudes toward this approach remain underexplored. We investigated Japanese psychiatrists' perceptions of combining atypical LAIs with psychosocial interventions. METHODS: An anonymous cross-sectional web-based survey was administered to 1038 mid-career Japanese psychiatrists, of whom 69 provided complete responses. Participants' general attitude toward recommending atypical LAIs was dichotomized as positive or negative/neutral, and they rated on a 4-point scale the usefulness of combining atypical LAIs with five psychosocial interventions: (1) psychosocial treatment (e.g., psychoeducation), (2) day/night care, (3) community care, (4) financial/employment support, and (5) housing support. RESULTS: Thirty-nine respondents held a positive attitude toward recommending atypical LAIs, whereas 30 held a negative/neutral attitude. A positive attitude was significantly associated with perceiving the combination as useful for psychosocial treatment (p = 0.038), financial/employment support (p = 0.015), and housing support (p = 0.041), but not for day/night care (p = 0.090) or community care (p = 0.079). Free-text rationales most commonly cited improved adherence and relapse prevention, enhanced illness insight, and synergistic effects as reasons for valuing the combination. CONCLUSIONS: This exploratory study suggests that mid-career Japanese psychiatrists, particularly those with a favorable attitude toward atypical LAIs, perceive the combination of LAIs with psychosocial support not merely as an adherence tool but as a synergistic strategy promoting broader functional recovery. Because respondents represent a small, predominantly male, self-selected sample, the generalizability of the findings is limited.
Amlexanox, a 5H-benzopyranopyridine derivative with emerging therapeutic potential in metabolic and inflammatory diseases, lacks a validated analytical method for pharmacokinetic studies in beagle dogs. A sensitive LC-MS/MS method was developed and validated for amlexanox in beagle dog plasma according to ICH M10 guidelines. Propranolol served as internal standard. Samples were processed by protein precipitation, and separation was achieved on a CAPCELL PAK C18 column using gradient elution with water and acetonitrile (both containing 0.2% formic acid) at 400 μL/min. Detection used positive electrospray ionization with MRM of m/z 299.0 → 281.0 for amlexanox and m/z 260.0 → 116.1 for IS. The method showed good linearity over 40-2000 ng/mL (R2 > 0.99). All validation parameters met acceptance criteria. The method was applied to a three-period fixed-sequence study in beagle dogs (n = 3, male) comparing intravenous injection (1 mg/kg), conventional tablets (75 mg), and sustained-release tablets (150 mg). The sustained-release formulation prolonged Tmax (3.67 vs. 1.00 h) and residence time (two-fold increase in t1/2 and MRT), and improved absolute bioavailability from 25.36% to 33.09% (relative bioavailability: 151.30%). These findings support the clinical development of a sustained-release amlexanox formulation with reduced dosing frequency and improved patient compliance.
The scarcity of effective therapies for Alzheimer's disease (AD) underscores the urgent need for innovative strategies. This review focuses on the targeted delivery of engineered small extracellular vesicles (sEVs, 30-150 nm). By capitalizing on their intrinsic properties as natural nanocarriers-including low immunogenicity and excellent biocompatibility-these EVs can be engineered to co-deliver therapeutic cargoes such as specific miRNAs, neurotrophic factors (e.g., BDNF), and nucleic acid modalities (e.g., siRNA/ASO targeting BACE1). While a single construct simultaneously delivering all these agents with proven in vivo synergy remains a conceptual framework rather than a validated reality, independent studies have demonstrated that EV-mediated delivery of each cargo type exerts beneficial effects on AD pathology, including Aβ clearance, Tau pathology alleviation, and neuroinflammation suppression. The intranasal administration offers a significant brain-targeting advantage by enabling direct nose-to-brain delivery, bypassing the blood-brain barrier and minimizing peripheral biodistribution. Recently, a phase I/II trial (Ruijin Hospital) demonstrated that intranasal MSC-EVs are safe and produce durable cognitive improvements (ADAS-Cog ↓ 2.33 points at week 12, sustained to - 3.98 points at week 36) in the medium-dose cohort, exceeding the minimal clinically important difference (MCID) of ≥ 2 points for AD. Based on these demonstrated clinical and preclinical evidence, we propose that rationally engineered EVs, following rigorous systematic pharmacology and safety assessments, hold transformative potential to pioneer a safe, efficacious, and non-invasive breakthrough therapy for AD, while acknowledging that critical challenges in GMP manufacturing, biodistribution, and regulatory approval remain to be resolved.
The AAPS journalChandrika Chaturvedi, Carman Giacomantonio, H P Vasantha Rupasinghe
Skin cancer continues to pose a significant global health burden, with conventional therapeutic modalities limited by systemic toxicity, poor tumor selectivity, and the development of therapeutic resistance. Glucosinolates (GLs) and their hydrolyzed product, sulforaphane, have attracted considerable interest as chemopreventive and therapeutic agents owing to their potent antioxidant, anti-inflammatory, and pleiotropic anticancer activities. However, the clinical translation of these phytochemicals is severely hindered by their chemical instability, rapid metabolism, and poor bioavailability. Nanocarrier systems, particularly biodegradable polymeric nanoparticles such as poly(lactic-co-glycolic acid) nanoparticles, offer a promising strategy to overcome these barriers by enhancing compound stability, improving bioavailability, and enabling tumor-targeted delivery via the enhanced permeability and retention effect. This review critically evaluates recent progress in the development of GL and sulforaphane-loaded nanocarriers, detailing their physicochemical properties, in vitro and in vivo anticancer efficacy, and safety profiles, highlighting their potential to advance more effective and less toxic therapeutic strategies for skin cancer prevention and treatment.
Breast cancer (BC) stands as a major medical concern for women because treatment hurdles include drug resistance combined with treatment failure and severe side effects and the intricate tumor microenvironment (TME). The treatment-resistant breast cancer subtype triple-negative breast cancer (TNBC) exhibits high aggressiveness through its failure to respond to targeted treatment yet maintains substantial metastatic potential. Hydrogels that react to stimuli have recently shown promise as solutions for solving these clinical issues. These hydrogels show response to precise stimuli which include pH, temperature and light and magnetic fields and biological elements including glutathione together with overexpressed enzymes MMP2 and MMP9 that appear within BC tumors. Hydrogel systems that respond to enzymes release drugs precisely at tumors thus minimizing drug side effects and optimizing their therapeutic effects. Hydrogel systems become more effective because of their ability to control drug delivery and combine various treatments when nanomaterials are incorporated as parts of their structure. Hydrogels must have adequate mechanical toughness because it enables them to withstand physical pressure without losing their drug release capabilities throughout the extended treatment period. This review has demonstrated that hydrogel-based drug delivery systems decrease tumor dimensions while inhibiting metastasis making them an advanced treatment strategy for BC management. The novel hydrogel platforms will lead to individualized treatment methods which show substantial promise to enhance breast cancer therapy results.
Daru : journal of Faculty of Pharmacy, Tehran University of Medical SciencesShweta Yadav, Prashant Singh, Madhusudan Purohit, Shashikant Singh, Shobha Singh
BACKGROUND: Diabetes mellitus, a chronic metabolic disorder affecting over 537 million individuals worldwide, represents one of the most burdensome global health challenges of the 21st century. Despite the availability of numerous oral antidiabetic agents, their therapeutic effectiveness is significantly compromised by poor aqueous solubility, chemical instability in the gastrointestinal (GI) environment, extensive hepatic first-pass metabolism, low membrane permeability, and inadequate systemic bioavailability. Nanotechnology-based drug delivery systems have emerged as transformative platforms capable of circumventing these multifaceted physiological and biopharmaceutical limitations. OBJECTIVE: This comprehensive review critically evaluates the landscape of nanostructured platforms designed to enhance oral bioavailability and therapeutic outcomes of antidiabetic agents, with particular emphasis on mechanistic insights into nanoparticle-epithelial interactions, surface functionalization strategies using targeting ligands (lectins, transferrin, folic acid, bile acid conjugates), and stimuli-responsive release mechanisms. METHODS: A structured literature search was conducted across PubMed/MEDLINE, Scopus, Web of Science, and ScienceDirect for articles published between January 2010 and 2026, with emphasis on publications from 2022 to 2026. We systematically analyzed and compared eleven distinct nanocarrier platforms, including polymeric nanoparticles, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), self-emulsifying drug delivery systems (SEDDS), liposomes, nanoemulsions, dendrimers, cyclodextrin inclusion complexes, mesoporous silica nanoparticles, metal-organic frameworks (MOFs), and hybrid nanocomposites, evaluating how each platform addresses specific absorption barriers including GI enzymatic degradation, mucus layer penetration, enterocyte uptake, and efflux pump activity. RESULTS: Rational formulation design, in vitro-in vivo correlations, and pharmacokinetic enhancement data indicate that nanoformulated antidiabetic drugs consistently outperform conventional formulations in bioavailability and absorption across multiple drug classes and delivery platforms. Emerging paradigms including exosome-inspired nanocarriers, CRISPR-integrated systems, and artificial intelligence-guided formulation optimization further extend the mechanistic and translational scope of oral nanomedicine for diabetes management. CONCLUSION: Nanostructured platforms offer a mechanistically diverse and increasingly translatable strategy for overcoming the physiological and biopharmaceutical barriers that limit oral antidiabetic therapy. Realizing their full clinical potential will require continued progress in addressing translational challenges, harmonizing regulatory frameworks, and advancing scalable manufacturing toward clinically viable oral nanomedicines for diabetes management.
Daru : journal of Faculty of Pharmacy, Tehran University of Medical SciencesAnurag Biswas, Bijoy Ghosh, Pallvi Kumari, Ankita Rangra, Kaunava Roy Chowdhury, Akshay Kumar
BACKGROUND: The human microbiome can actively influence how drugs are handled and processed in our body. More knowledge of host-microbiome-drug interactions has shifted drug delivery from current approaches to precision therapeutics. OBJECTIVES: The review is to evaluate various targeted strategies and mechanisms of drug delivery systems (DDS) driven by pharmacomicrobiomics. Moreover, the pharmacomicrobiomics-based DDS will also be discussed in terms of their therapeutic applications, translation, and new technologies for microbiome precision. METHODS: Assessment on the latest development on microbiome-drug interactions and microbiome-based drug delivery strategies, including microbial enzyme activated prodrugs, nano- and micro-particle systems, probiotics, prebiotics, postbiotics, bacteriophages, genetically modified microorganisms, smart materials, and niche-selective delivery systems. The researchers also investigated clinical evidence, security, regulatory issues, Pharmacoeconomics and new emerging multi-omics and AI based strategies. RESULTS: Microbiome-targeted DDS enable localized drug activation, site-specific delivery, and reduced systemic exposure. Enzyme-responsive systems achieved up to a 3-fold increase in local drug concentration, while SER-109 (VOWST) reduced CDI recurrence to 12% versus 40% with placebo at 8 weeks. FMT combined with pembrolizumab achieved objective responses in 40% (6/15) of previously non-responsive melanoma patients. Engineered microbial therapeutics, including SYNB1618 and AG013, further demonstrate the growing translational potential of programmable microbiome-based therapies. CONCLUSION: Pharmacymicrobiomics-driven drug delivery systems (DDS) represent an innovative approach to precision therapeutics utilizing microbes. However, challenges such as individual microbiome variability, unvalidated biomarkers, safety concerns, intricate regulatory hurdles, and inconsistent translational outcomes from preclinical studies persist. A comprehensive integration of omics data and interdisciplinary collaboration is essential to enhance the predictability of microbiome therapies. Future efforts should focus on microbiome profiling, validating mechanism-based biomarkers, scalable manufacturing, and conducting clinical studies to define patient selection, ensure therapeutic consistency, and confirm long-term benefits.
Annals of medicineXinyun Tu, Youni Zhang, Li Wang, Yiyi Shan, Lihong Xie, Huafeng Shou, Yan Liang
BACKGROUND: Ovarian, cervical and endometrial cancers have been the leading cause of morbidity and mortality in women, often resulting from late diagnosis, resistance to therapies and off-target toxicity of conventional therapies. DISCUSSION: The review discusses recent progress in the development of dual-targeted nanocarrier systems in gynaecologic oncology, relying on peer-reviewed publications in scientific databases published within the past decade. Applications of these systems are also discussed in terms of the potential to improve the selectivity and therapeutic efficiency of tumour therapy. Major available evidence is based on preclinical in vitro and in vivo models. Clinical translation is in its early-phase trials, suggesting clinical validation in gynaecologic oncology remains in its infancy. The most important challenges in translation are scalable manufacturing, long-term safety, biological complexity and regulatory challenges. CONCLUSION: This review describes the prevailing situation and constraints of dual-targeted nanotechnology, focusing on possible applications in the development of more accurate and individualized therapies for gynaecologic cancers.
Human vaccines & immunotherapeuticsMuhammad Inam, Muhammad Jamshed, Abuzar Osman
Nanotechnology has transformed vaccine development by engineering nanovaccines that offer precise control over antigen performance, immune modulation and targeted delivery. These platforms influence physicochemical properties size, charge, and ligand expression to direct antigen trafficking, co-deliver adjuvants and antigen-presenting cells, stimulating potent and robust adaptive immune responses. This review discusses the development of nanovaccines for prophylactic vaccines which induce antibody and memory B-cell responses and therapeutic cancer vaccines, which overcome tolerance and immunosuppression to activate CD8+ T cells with particular emphasis on lipid nanoparticles (LNPs), polymeric NPs, inorganic-core NPs, virus-like particles (VLP) and mechanisms by which each platform exploits physicochemical properties to enhance the antigen encapsulation, adjuvant incorporation, lymphatic transferring, quality and quantity of adaptive immune responses. We reviewed the clinical and preclinical developments of these nanovaccine platforms in cancer and infectious disease immunotherapy, including major successes and new opportunities that will shape the future of vaccines for prevention and treatment.
International journal of nanomedicineJunhui Qian, Siqi Shen, Sijia Chen, Hua Zhang, Lianliang Liu, Dezheng Zhou, Xiaohong Zhang
Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory disorder with a complex etiology and a high recurrence rate. Conventional treatments face significant limitations in targeting, stability, and efficacy. Going beyond conventional reviews that focus on isolated mechanisms, this review offers a systematic integration of three engineering perspectives: how to deliver (targeting mechanisms), what to deliver (pathology-based therapeutic payloads), and what to use for delivery (smart material design). We highlight emerging nanoplatforms-including nanozymes, probiotic-based nano-delivery systems, and stimuli-responsive nano-delivery systems-that address oxidative stress and gut dysbiosis, two core pathologies of IBD. We also discuss novel approaches for delivering nanodrugs to target cells and advocate for the use of hybrid synthetic/natural materials to achieve a balance between efficacy and safety of nanomaterials. However, a critical gap that must be confronted is that the vast majority of existing studies remain confined to acute, chemically induced colitis models (typically 7-14 days), which poorly recapitulate the chronic, relapsing nature of human IBD. Systematic validation of long-term safety and efficacy including biodistribution, metabolic clearance, and chronic toxicity profiles over extended periods is urgently needed before any meaningful clinical translation can be contemplated. This recognition of the acute-to-chronic translation gap constitutes a central critical stance of this review. This is not merely a methodological concern but a fundamental barrier that pervades the entire field: the disconnect between acute model readouts and chronic disease outcomes has systematically inflated translational expectations while masking the true challenges of long-term efficacy, safety, and durability. Addressing this gap requires not only acknowledging its existence but also implementing concrete, standardized protocols for chronic model evaluation. Multidisciplinary collaboration is urgently needed to accelerate clinical translation.
The present study explores the potential of sorafenib (SOR) and atorvastatin (ATST) to induce a ferroptosis and apoptosis-based hybrid cell death mechanism. The synergistic ATST + SOR combination was delivered through Glutamine-tagged PLGA nanoparticles (ATST + SOR/G-PLGA NPs) to promote intratumoral specificity. The formulation was optimized using DesignExpert® software by adopting Box-Behnken design (BBD). The optimized ATST + SOR/G-PLGA NPs had a spherical particle size of ~ 178.3 ± 12.6 nm, a PDI of 0.151 ± 0.08, and a Z-potential of -24.8 ± 5.8 mV. The formulation revealed a biphasic sustained release with higher release at acidic pH. In-vitro biological assessment showed a dose-dependent decrease in cell viability with reduced IC50 values. In the presence of ferrostatin-1, the IC50 value was significantly increased. The exposure to ATST + SOR/G-PLGA NPs led to elevated levels of malondialdehyde (MDA), reactive oxygen species (ROS), glutathione (GSH), increased late apoptotic/necrotic cells, and mitochondrial membrane depolarization. Pharmacokinetic study revealed a 2.63- and 2.93-fold improved AUC0-∞, and 2.58- and 2.84-fold improvement in MRT as compared to free SOR and ATST. Preclinical efficacy study showed a marked reduction in tumor volume and a higher inhibition rate. Toxicity assessment revealed no signs of systemic or organ toxicity, implying suitability of formulation for in-vivo delivery. In a nutshell, the proposed strategy offers a powerful avenue to manage advanced malignancies by inducing a hybrid cell death mechanism. Also, the nutrient transporter targeted polymeric nanosystems present an effective approach, which warrants further investigation.
International journal of nanomedicineHang Zhang, Jia Guo, Xinmiao Wang, Yuchen Shen, Yijie Yao, Sushilkumar Shivaji Ghadage, Sainath Kamble, Sami A Al-Hussain, Magdi E A Zaki, Shravan Jadhav, Vija…
The clinical translation of cancer nanomedicine remains constrained by inefficient intracellular delivery, poor subcellular specificity, and limited tumor accumulation, highlighting the need for more precise drug delivery strategies. Organelle-targeted nanocarriers have emerged as a promising platform for enhancing therapeutic efficacy by directing drugs to specific intracellular compartments, including the nucleus, mitochondria, lysosomes, and endoplasmic reticulum. However, the design principles governing efficient organelle-specific delivery and the barriers limiting clinical translation remain incompletely understood. This review provides a mechanistic framework linking nanoparticle physicochemical properties-including size, surface charge, ligand functionalization, and stimuli responsiveness to intracellular trafficking, organelle targeting, and therapeutic performance. We critically discuss the biological barriers encountered during delivery, including cellular uptake, endosomal escape, cytosolic transport, and organelle membrane penetration, together with current engineering strategies to overcome these challenges. Organelle-specific targeting approaches are comparatively evaluated to highlight their therapeutic advantages, limitations, and suitable clinical applications. Beyond summarizing recent advances, this review examines the major translational hurdles that impede clinical implementation, including non-specific biodistribution, manufacturing scalability, regulatory challenges, and the lack of standardized preclinical evaluation models. Emerging solutions such as hierarchical targeting, charge-reversal systems, size-transformable nanocarriers, and multifunctional theranostic platforms are discussed as strategies to improve clinical feasibility. Finally, we propose practical design guidelines and future research priorities that integrate nanomaterial engineering, predictive biological models, and scalable manufacturing to facilitate the development of clinically translatable organelle-targeted nanomedicines.
European journal of pediatricsWei Li, Hongxia Zhang, Qing Li, Deqing Kong
BACKGROUND: Pediatric diabetic ketoacidosis (DKA) is life-threatening; traditional IV insulin risks hypoglycemia and electrolyte issues. We evaluated the efficacy and safety of continuous subcutaneous insulin infusion (CSII) combined with electrolyte supplementation in DKA. METHODS: Sixty-six patients were randomly assigned to the study group (CSII + electrolyte supplementation) or control group (intravenous insulin infusion + electrolyte supplementation). Overall efficacy, time to pH normalization, target blood glucose achievement, urine ketone clearance, levels of BUN, creatinine, potassium, FPG, 2hPG and sodium, inflammatory markers, acid-base balance indicators, and adverse reactions were compared. RESULTS: Study group had higher overall efficacy (χ2 = 5.121), shorter time to pH normalization, target blood glucose achievement, and urine ketone clearance (t = 8.023, 7.712, 7.438), lower BUN, creatinine, FPG, 2hPG, sodium, CRP, TNF-α, and IL-6 levels (t = 8.893, 15.816, 5.865, 12.267, 4.542, 3.626, 2.615, 5.746), higher serum potassium, CO₂CP, and blood pH levels (t = 9.737, 4.220, 17.78), and lower blood lactate levels (t = 6.922) and adverse reaction rates (χ2 = 4.243) than the control group (all P < 0.05). CONCLUSION: CSII with electrolyte supplementation improves pediatric DKA treatment outcomes by regulating blood glucose and electrolytes, alleviating inflammation and acidosis, and reducing adverse reactions during treatment. WHAT IS KNOWN: • Pediatric diabetic ketoacidosis (DKA) is a life-threatening acute complication of diabetes mellitus. • Traditional intravenous insulin infusion is the standard treatment but carries risks of hypoglycemia, hypokalemia, and other electrolyte disturbances. • Electrolyte supplementation is routinely used alongside insulin therapy to correct dehydration and metabolic imbalances in DKA. WHAT IS NEW: • This study provides clinical evidence that continuous subcutaneous insulin infusion (CSII) combined with electrolyte supplementation is more effective than conventional intravenous insulin therapy in pediatric DKA. • CSII-based regimen achieved faster pH normalization, blood glucose control, and urine ketone clearance, with better improvements in renal function, inflammatory markers, and acid-base balance. • The CSII group also showed lower rates of adverse reactions, suggesting that this approach may offer a safer and more efficient alternative for managing pediatric DKA.
Lasers in medical scienceAya Fahim, Elham Saied, Marwa S El-Mesidy
Burns result in hypertrophic scarring, causing functional impairment, cosmetic and psychological concerns. Fractional CO₂ laser and botulinum, have shown promise in treatment. To evaluate the effectiveness of fractional laser treatment alone and combined with botulinum toxin A, delivered either through injections or topical application as fractional laser-assisted drug delivery in hypertrophic burn scar. A randomized comparative trial involving 16 patients with post-burn hypertrophic scars. The scar of each patient was divided into 3 sections: (1) fractional CO₂ laser combined with intralesional botulinum toxin type A, (2) fractional CO₂ laser monotherapy, and (3) fractional CO₂ laser with laser-assisted drug delivery of BTXA. Patients received three treatment sessions at monthly intervals, followed by a three-month follow up. Clinical outcomes were evaluated using the Vancouver Scar Scale. Intralesional BTXA demonstrated superior efficacy, achieving the greatest reductions in VSS (- 58.25%). Intralesional BTXA in combination with fractional CO₂ laser represents a highly effective treatment for post-burn hypertrophic scars, offering superior improvements in scar pliability, contour, and patient comfort compared with laser monotherapy or LADD. These findings support intralesional BTXA as the preferred therapeutic approach, while highlighting the potential of combination protocols for optimizing scar outcomes.
Journal of biomedical materials research. Part AEda Ciftci, Sefa Burak Cam, Feza Korkusuz, Emre Erdem, Feray Bakan Misirlioglu, Petek Korkusuz
Calcium phosphates alone have a limited induction potential in challenging bone conditions, necessitating strategies that enhance cellular responses and matrix-related processes. An injectable formulation combining calcium-deficient hydroxyapatite (CDHA) with mesenchymal stem cell-derived extracellular vesicles may present a promising approach for modulating osteogenic activity. A dual formulation composed of calcium-deficient HA and human bone marrow mesenchymal stem cell-derived extracellular vesicles, incorporating Annexin V as a binding molecule, was generated and validated. Structural and molecular characterization was performed using Raman spectroscopy, electron paramagnetic resonance, and sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Real-time impedance-based cell proliferation analysis was applied to determine biologically effective concentrations. The effects of the formulation on human osteoblast behavior and early osteogenic activity were additionally evaluated. Raman spectroscopy confirmed structural integration within the formulation termed CHAnEx, showing peak shifts and spectral features at 959, 630, and 806 cm-1, indicating molecular interactions between calcium-deficient HA, Annexin V, and extracellular vesicles. Electron paramagnetic resonance (EPR) analysis revealed distinct g-factor shifts consistent with binding interactions. Real-time proliferation analysis identified biologically effective concentrations of calcium-deficient HA and extracellular vesicles using human osteoblast models. The combined formulation increased alkaline phosphatase activity, showing approximately a 20%-25% increase compared to control groups. These findings indicate that the calcium-deficient HA-extracellular vesicle formulation supports functional interactions and modulates osteoblast responses under in vitro conditions, suggesting its relevance as an injectable biomaterial platform.
Journal of food scienceMuhammad Umair Khalid, Khubaib Ali, Eihab Hatem JadElrab, Dina M El-Sherif, Hang Yu, Weirong Yao
This study developed a chitosan/pullulan composite film (CS/PULL CF) incorporating pullulan-based anisaldehyde/cinnamaldehyde nanocapsules (PULL-ANIS/CIN NC) for bread preservation. The effects of PULL-ANIS/CIN NC concentrations from 0% to 2.0% (w/v) on the physicochemical, structural, antioxidant, antimicrobial, and release properties of the films were evaluated, together with their performance during 15 days of bread storage. The results demonstrated that increasing the concentration of PULL-ANIS/CIN NC led to gradual thickening, increased surface roughness, and a yellowish appearance of the film. Correspondingly, water resistance, barrier performance, tensile strength, antioxidant, and antimicrobial properties improved, whereas elongation at break and UV-Vis transmittance decreased. The CS/PULL CF containing 2.0% (w/v) PULL-ANIS/CIN NC showed the best overall performance, with water vapor permeability of 1.78 ± 0.00 g·mm/m2·h·kPa, oxygen permeability of 0.37 ± 0.01 cc/m·24 h·atm, water contact angle of 86.0° ± 0.87°, tensile strength of 8.65 ± 0.03 MPa, and elongation at break of 27.73% ± 1.41%. FTIR, XRD, and TGA analyses confirmed good compatibility between PULL-ANIS/CIN NC and the CS/PULL matrix. Release data fitted the Ritger-Peppas and Peppas-Sahlin models well (adjusted R2 > 0.90) and were predominantly governed by Fickian diffusion. The 2.0% film also provided the best bread preservation performance, with favorable microbial, textural, LF-NMR, and E-nose characteristics. These findings demonstrate the potential of PULL-ANIS/CIN NC-loaded CS/PULL CF as sustainable active packaging for bakery products.
Delivering hydrophobic active pharmaceutical ingredients remains a major challenge due to poor aqueous solubility, limited bioavailability, and chemical instability. Drug-in-cyclodextrin-in-liposome (DCL) technology combines cyclodextrin inclusion complexation with liposomal encapsulation to address these limitations. In this hybrid approach, the hydrophobic drug is first incorporated into the apolar cyclodextrin cavity, and the resulting complex is subsequently encapsulated within the aqueous compartment of liposomes. This review provides a comprehensive, data-driven analysis of DCL technology, covering its conceptual development, cyclodextrin properties, lipid composition, vesicle architecture, and preparation methods. Quantitative parameters, including encapsulation efficiency, particle size, zeta potential, and drug release, are compared with conventional liposomes and cyclodextrin complexes. DCL systems demonstrated 2 to 11 fold higher encapsulation efficiency than conventional liposomes, together with sustained release, improved vesicle stability, and enhanced protection of labile drugs against degradation. Preclinical evidence indicates potential therapeutic benefits, although in vivo validation remains limited. Molecular docking and molecular dynamics further provide mechanistic insights into drug-cyclodextrin and cyclodextrin-membrane interactions. Emerging strategies include surface modification, stimuli-responsive systems, dual-drug loading, green manufacturing, and computational design, supporting the future clinical translation of DCL technology.
Macromolecular bioscienceJun Ma, Ruochen Liu, Ibrahim Chamseddine, Jingjing Qiu, Shiren Wang
Poor penetration into tumor tissue remains a major barrier to effective nanomedicine delivery, particularly in glioblastoma multiforme (GBM). Here, nanoparticle transport was computationally studied to rationally design an ultrasmall chemotactic nanomotor that improves penetration into dense tumor tissue. The nanomotor comprises a targeting human heavy-chain ferritin (HFn) nanocage and a catalytic cerium oxide (CeO2) component. Leveraging transferrin receptor‑1 overexpression on brain microvascular endothelial cells and GBM cells, HFn enables transport across an in vitro blood-brain barrier (BBB) model and accumulation in GBM spheroids. The CeO2 domain catalyzes hydrogen peroxide decomposition in the tumor‑mimicking microenvironment, generating oxygen and imparting directional propulsion along H2O2 gradients. In chemotaxis assays, the nanomotors actively migrated toward localized H2O2 sources and GBM cells embedded in Matrigel. In large U87 spheroids (>400 µm), HFn@CeO2 nanomotors penetrated deeply and distributed throughout the spheroid core, whereas non‑propelled HFn nanocarriers remained confined mainly to the periphery. Doxorubicin‑loaded nanomotors (HFn@CeO2-DOX) achieved substantially enhanced intratumoral DOX distribution and reduced IC50 (0.33 µM) compared with HFn-DOX (1.13 µM) and free DOX (1.75 µM) in GBM spheroids. These results provide a promising basis for future in vivo evaluation in brain tumor therapy.
Pakistan journal of pharmaceutical sciencesAmina Arshad, Muhammad Zaman, Humayun Riaz, Muhammad Sajjad Haider, Wafa Ishaq, Sherjeel Adnan, Zeeshan Masood, Hammad Ahmed, Nabeela Ameer, Hafiz Muhammad Abd…
BACKGROUND: Pitavastatin (PVN), a BCS class-II drug, exhibits poor aqueous solubility leading to limited oral bioavailability and therapeutic efficacy. OBJECTIVES: This study aimed to enhance the solubility and anti-hyperlipidemic efficacy of Pitavastatin (PVN) by encapsulating it in chitosan-based polymeric nanoparticles. METHODS: Pitavastatin-loaded chitosan nanoparticles (NPs) were prepared using the ionic gelation method. Formulations were characterized by particle size, zeta potential, drug loading, In-vitro drug release and surface morphology. Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermal analysis (TGA and DSC), ex-vivo intestinal permeability and in-vivo pharmacodynamic analysis were also performed. RESULTS: The size of PVN-loaded NP ranged from 219.9±1.11 to 292.7±2.29 nm with PDI 0.2-0.4, surface charge of +28.4 ± 0.43 to 32.5 ± 1.02 mV and entrapment efficiency 65±1.12-93±1.23%. Solubility in different media (PBS (pH 6.8), 0.1N HCl (pH 1.2) and distilled water showed a 56-102-fold increase compared to PVN. SEM analysis revealed a smooth surface and spherical geometry of the NP. FTIR analysis confirmed that there was no physicochemical interaction between PVN and chitosan in NP formulations (NP1-NP5). XRD and thermal analysis indicated the amorphous nature of PVN-loaded NP. In-vitro drug release from NP formulations (NPI-NP5) ranged from 80.97±4.80 to 81±3.90% indicating sustained release, while ex-vivo intestinal permeability was 1.5-fold higher than PVN. The optimized formulation (NP1) followed Higuchi release model, indicating Fickian diffusion. Pharmacodynamic analysis of lipid profiles in hyperlipidemic albino rats suggested that NP1 reduced low-density lipoprotein (LDL) by 33±1.24 %, total cholesterol by 29±2.13% and triglycerides by 23±1.21%, showing better results than PVN. CONCLUSION: Chitosan-based Pitavastatin nanoparticles successfully enhanced drug solubility and provided sustained release, leading to improved ex-vivo permeability and greater in-vivo anti-hyperlipidemic activity in albino rats. This approach represents a promising strategy for enhancing therapeutic potential of Pitavastatin.
Experimental dermatologyFabiana Boncimino, Stefano Sol, Kristina Todorova, Anna Mandinova
Skin aging is a multifactorial process characterized by the progressive decline of tissue structure, function and regenerative capacity. Although numerous interventions have been developed to improve the clinical manifestations of aging, most primarily alleviate downstream consequences rather than directly targeting the molecular mechanisms underlying tissue deterioration. Recent advances in single-cell and spatial transcriptomic technologies have fundamentally transformed our understanding of skin aging by identifying cell type-specific transcriptional programmes and uncovering novel regulators of epidermal homeostasis, dermal remodelling and intercellular communication. These high-resolution atlases have generated an expanding repertoire of candidate rejuvenation targets, many of which consist of intracellular regulatory proteins that have traditionally been considered difficult to manipulate using conventional pharmacological approaches. In parallel, rapid progress in RNA engineering has established nucleic acid therapeutics as a versatile approach for precise molecular intervention. Among these, messenger RNA (mRNA) therapeutics are particularly well suited to the molecular landscape emerging from skin aging atlases because they enable transient restoration of proteins that are lost during aging. Advances in lipid nanoparticles, extracellular vesicles and microneedle-based delivery systems are rapidly improving the feasibility of local cutaneous administration. In this review, we discuss the emerging rejuvenation targets identified by single-cell and spatial transcriptomic atlases and examine recent advances in RNA-based therapeutics and mRNA delivery strategies that are paving the way for precision skin rejuvenation.
Drug deliveryYoungbeom Kim, Chae-Ok Yun, A-Rum Yoon
Nose-to-brain (N2B) delivery is a promising noninvasive strategy to circumvent the blood‒brain barrier (BBB). However, the clinical translation of N2B platforms remains hindered by a conceptual oversimplification that equates crude central nervous system (CNS) exposure with effective therapeutic delivery. This review reconceptualizes the N2B pathway as a stage-resolved sequential transport cascade extending from nasal entry to meaningful parenchymal and cellular access. We identify a critical imbalance in current formulation strategies, which have advanced two extreme poles, namely initial mucosal retention and epithelial permeation at one end and final target-cell engagement at the other, while leaving the intermediate post-epithelial gateways, including cerebrospinal fluid (CSF) and perivascular space (PVS)-mediated redistribution and deep intraparenchymal diffusion, as structural and interpretive blind spots. To bridge this gap, we propose an integrated engineering paradigm with three core design principles. First, multistage-aware design harmonizes sequential spatiotemporal functionalities within a single vehicle architecture. Second, disease-informed design integrates pathologically remodeled barrier states and glymphatic hydrodynamics into the formulation rationale. Third, cargo-informed design establishes the distinct biophysical identity and inherent liabilities of each payload, from small molecules to viral vectors and CRISPR machinery, as the primary engineering starting point. Finally, we advocate for a methodological standard demanding stage-specific validation of vehicle integrity, cross-boundary penetration, and functional target engagement, beyond compartment-blind whole-brain readouts. We further underscore the biofate and clearance of delivery systems as an emerging axis of safety and regulatory evaluation. Collectively, this framework provides a systematic basis for transitioning N2B engineering into a viable clinical modality.
This study aimed to develop and validate an injectable thermosensitive hydrogel as an ultrasound-responsive depot for transiently enhanced BMP-2 release to promote functional and structural recovery in a rat model of osteoarthritis. A BMP-2-loaded mPEG-PLGA-BOX thermosensitive hydrogel was developed and characterized in vitro for its rheological properties, degradation behavior, and drug-release kinetics. The feasibility of ultrasound-triggered release was assessed using various duty cycles. Subsequently, therapeutic efficacy was evaluated in a monoiodoacetate-induced rat model of osteoarthritis. Treatment groups included untreated control (MIA), free BMP-2 (MB), passive BMP-2-hydrogel (MHB), and BMP-2-loaded hydrogel with ultrasound stimulation (MHBU). Outcomes were assessed up to day 49 using functional gait analysis (CatWalk), histopathology (H&E, Toluidine Blue), and immunohistochemistry for Collagen II, Collagen X, and Sox 9. The in vitro analysis supported the selection of a non-thermal 5% ultrasound duty cycle, which produced an approximately 550-fold ultrasound-enhanced release ratio without a detectable temperature increase while limiting residual-volume loss relative to the higher-duty-cycle conditions. In vivo, the MHBU therapy was uniquely effective. It was the only intervention to significantly restore articular cartilage thickness (212.8 ± 42.0 μm vs. 124.3 ± 12.7 μm, p < 0.01), achieving a level statistically indistinguishable from healthy controls. This structural repair was directly correlated with normalized dynamic gait parameters (print area, stance) and a restored tissue-level profile, characterized by enhanced Collagen II matrix, suppressed pathological Collagen X expression, and recovered chondrogenic Sox 9 expression. This study demonstrates that an ultrasound-responsive hydrogel platform successfully overcomes the limitations of both conventional growth factor delivery (rapid clearance) and passive hydrogel encapsulation (slow release). This synergistic, ultrasound-triggered system promotes significant functional and structural cartilage restoration, representing a promising translatable strategy for osteoarthritis therapy.
In situ cancer vaccines exhibit promising therapeutic potential; however, their efficacy is constrained by limited antigen release, suboptimal spatiotemporal immune coordination, and adaptive immune resistance. In this study, we identify zinc ions (Zn2+) as synergistic agents with chemotherapeutics in modulating PANoptosis and immune signaling pathways. Capitalizing on this concept, a chemo-metallic nanodriver was developed for effective in situ cancer vaccination. This system used zinc-aluminum layered double hydroxides as the structural base and efficiently loaded cisplatin (DDP) and indocyanine green via coordination-driven polymerization, forming a spatiotemporally controllable nanodriver, which facilitated the simultaneous release of drug and metal ions upon photoactivation. The released Zn2+ specifically disrupted zinc homeostasis in tumor cells, inducing mitochondrial dysfunction. This effect acted in concert with DDP-mediated DNA damage, not only effectively activating the cGAS-STING (cyclic GMP-AMP synthase-stimulator of interferon genes) pathway but also promoting the assembly and activation of AIM2-PANoptosome complex to execute PANoptosis. This STING-PANoptosis cascade led to a burst release of damage-associated molecular patterns, markedly enhanced dendritic cell maturation, and stimulated the secretion of pro-inflammatory cytokines. Furthermore, the nanodriver elicited a robust antitumor immune response and established durable immune memory in mouse models. These findings not only provide an optimized strategy for precise immunotherapy of gastric cancer but also increase the understanding of the applications of metal ion immunology and PANoptosis in disease intervention.
Neurological disorders represent a major global health burden, primarily due to the limited ability of therapeutic agents to cross the blood-brain barrier (BBB). Nose-to-brain (NTB) delivery has emerged as a promising non-invasive strategy to bypass the BBB and directly target the central nervous system (CNS). Among various polymers, chitosan has gained significant attention owing to its favourable physicochemical properties, biocompatibility, biodegradability, mucoadhesive nature, and ability to transiently open tight junctions of the nasal epithelium. This review comprehensively discusses the potential of chitosan-based systems for NTB delivery in the management of neurological disorders. The article outlines the physicochemical properties and biomedical applications of chitosan, followed by a detailed discussion of nasal anatomy and transport pathways involved in NTB drug delivery. The pharmacological aspects of chitosan in neurological disorders are highlighted, including its anti-oxidative, anti-neuroinflammatory, anti-apoptotic, anti-excitotoxic effects, suppression of β-amyloid accumulation, and acetylcholinesterase inhibitory activity. Various formulation approaches are critically reviewed, including chitosan-based nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, liposomes, microparticles, microspheres, and in situ gels designed for intranasal administration. Furthermore, surface-modified chitosan systems aimed at enhancing brain targeting are discussed, such as PEGylation, ligand-conjugated chitosan (transferrin and lactoferrin), cell-penetrating peptide functionalization, thiolated chitosan, and pH-sensitive derivatives including carboxymethyl and N-trimethyl chitosan. Comparative tables summarize formulation strategies, neurological indications, biological models, key outcomes, and reported findings. Overall, this review highlights the significant potential of chitosan and its surface-engineered derivatives as versatile carriers for NTB delivery in neurological disorders.
Triple-negative breast cancer (TNBC) is an aggressive subtype with limited therapeutic options and poor clinical outcomes. This study evaluated folic acid-functionalized solid lipid nanoparticles co-loaded with docetaxel and erlotinib (FA-DOC/ERL-SLNs) as an oral targeted therapy for TNBC. FA-DOC/ERL-SLNs exhibited the lowest IC₅₀ values of 0.82 ± 0.05 μM and 0.92 ± 0.03 μM in MDA-MB-231 and 4T1 cells, respectively, with enhanced cellular uptake compared with free drugs and non-targeted SLNs. The formulation also induced higher apoptosis (apoptosis indices of 1.42 and 1.45), greater G2/M cell-cycle arrest, autophagy inhibition, and reduced clonogenicity and migration. Pharmacokinetic studies demonstrated markedly improved oral bioavailability, with AUC₀-t increasing from 1.03 to 45.69 μg·h/mL for docetaxel and from 18.30 to 87.76 μg·h/mL for erlotinib. In 4T1 tumor-bearing mice, FA-DOC/ERL-SLNs reduced tumor volume by approximately 1.5-fold compared with non-targeted SLNs and 2.5-3.0-fold compared with free drugs, without significant body weight loss or systemic toxicity. These findings demonstrate that FA-DOC/ERL-SLNs enhance the efficacy and safety of oral docetaxel-erlotinib combination therapy and represent a promising targeted nanocarrier platform for TNBC treatment.
AAPS PharmSciTechRaghda Abd El Moneum Ali Abdel Mawla, Wedad Sakran, Fares Ibrahim Farag Masry, Mohammed Salah Ahmed Teiama
This study was designed to develop and optimize a thermosensitive intranasal gel incorporating temozolomide (TMZ) and N-acetylcysteine (NAC) as a promising platform for direct nose-to-brain drug delivery. Formulations were fabricated via cold technique utilizing Carbopol 934P and poloxamer 407 to improve gelation and mucoadhesion. After evaluating the formulations for clarity, pH, gelation temperature, gelling time, mucoadhesion, and drug loading, the formula A13 was elected as the optimized formulation based on a factorial design optimization approach. The optimized formula was further evaluated for stability, ex-vivo permeability, histopathology and in-vivo pharmacokinetic in rats. Compared with the corresponding in-situ gels containing the pure drugs, formulation A13 enhanced the ex-vivo nasal mucosal permeation of TMZ and NAC by 1.42-fold and 1.64-fold, respectively, indicating the superior permeability-enhancing effect of A13. Furthermore, histopathological examination revealed no evidence of structural damage following administration of formulation A13, confirming its safety for intranasal application. The in-vivo studies performed on rats showed significantly higher Cmax and AUC 0-24 results in brain of the optimized A13 by 1.4, 1.4, 2.6 and 1.87 folds in TMZ and NAC, respectively compared to in-situ gel of pure TMZ and in-situ gel of pure NAC, with a delayed (Tmax). The brain-to-blood concentration ratios of the TMZ-NAC-loaded in-situ gel were consistently higher than those of the pure-drug in-situ gels at most sampling time points, indicating more efficient nose-to-brain transport. Overall, these findings demonstrate that the optimized A13 is a promising and safe intranasal delivery system for enhancing the nose-to-brain delivery and bioavailability of TMZ and NAC.
In vitro dissolution testing is central to pharmaceutical development, yet it is increasingly challenged by poorly soluble drugs, which account for over 40% of marketed products and up to 90% of new chemical entities, for which dissolution often limits absorption. Surfactants are widely incorporated into dissolution media to achieve sink conditions and improve the discriminatory powder of dissolution methods, but inappropriate surfactant selection or concentration can alter drug release mechanisms, mask formulation differences, and reduce biopredictive performance. This review examines the mechanisms of surfactant action, including wetting enhancement, micellar solubilization, and drug-surfactant interactions, together with the physicochemical properties of anionic, cationic, non-ionic, and zwitterionic surfactant relevant to dissolution testing. Building on these principles, we discuss practical considerations for surfactant selection, concentration optimization, analytical compatibility, surfactant quality and source variability, formulation-specific considerations for enabled drug delivery systems, integration with physiologically based biopharmaceutics modeling, and evolving regulatory expectations. Together, these provide a practical framework for developing robust, reproducible, and discriminating dissolution methods that better reflect in vivo performance and support decision-making across drug development.
AAPS PharmSciTechMagdi E A Abobaker, Mershen Govender, Yahya E Choonara
The therapeutic efficacy of interferon alpha (IFNα) is well-established in various conditions, including Hepatitis B and C, lymphoma and skin cancer, attributed to its potent angiostatic, immunomodulatory, and antiproliferative properties. Clinical applications using this bioactive are, however, hindered by systemic toxicity due to the high doses used, increasing costs and reducing patient adherence. The use of a controlled-release polymeric nanoparticulate system that can potentially decrease the administered dose, and therefore the associated costs, may additionally improve overall patient acceptability without affecting therapeutic efficacy. This study provides for the development, statistical optimization and characterization of poly(lactic-co-glycolic acid) nanoparticles (PLGANPs) for the controlled release of IFNα. A double-emulsion solvent evaporation method was employed for nanoparticle (NP) synthesis, with formulation optimization achieved through a Central Composite Design (CCD) approach to ensure adequate size, stability, and sustained release over five days. Characterization of the optimized IFNα-PLGANPs using dynamic light scattering, zeta potential analysis, scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and drug release studies at pH 7.2 displayed an average particle size of 97.03 nm (PDI = 0.182), zeta potential of - 34.10 mV and a maximum drug release of 5 days, with morphological analysis revealing the formation of spherical NPs with a smooth surface topology, confirming the homogeneity and structural stability of the formulation. These findings underscore the potential of the developed PLGANPs as a suitable platform for the controlled release of IFNα, noting the use of advanced nanotechnology-driven solutions to overcome the limitations of conventional therapies.
AAPS PharmSciTechKarmani Murugan, Pradeep Kumar, Lisa C du Toit, Poornima Ramburrun, Yahya E Choonara
Neogeometric copper nanoparticles (CuNPs) in drug delivery can be exploited for its cytotoxic effects and enhanced cellular uptake in dermatological conditions. The nanosystem, designed herein, is embedded in a Self-Oscillating Polymeric Network (SOPN) to stimulate the permeation of cubic CuNPs across the stratum corneum of induced psoriasiform-plaques in a BALB/c mouse model. Polymerization and cross-linking of the SOPN from NIPAM (N-isopropylacrylamide) and a metal salt exerted thermal and molecular differences of the resulting poly-NIPAM whilst maintaining inherent NIPAM thermo-responsive properties to control CuNP-permeation in an inflammatory environment. From an experimental design consisting of 15 formulations, it was found that thermo-responsive changes between 27-35˚C in the SOPN promoted the oscillatory behavior required for skin permeation of CuNPs where an oscillatory duration of 40 min was obtained. Viability analysis of the SOPN established biocompatible concentrations of the system for use in the in vivo model at reduced CuNP concentrations to control cytotoxicity (64.26-72.58%). The CuNP-loaded SOPN gel (60ug/mL) effectively promoted psoriatic-plaque resolution and hair growth, after 7 and 14 days of treatment, compared to the comparative (0.5% hydrocortisone cream). The geometric nanosystem embedded in an aqueous cream vehicle and the SOPN gel exhibited promising results in the reduction of in vivo psoriasiform-plaques compared to the gold standard.
Statins are widely regarded as the gold standard first-line treatment for hyperlipidemia, as they inhibit HMG-CoA reductase in the liver. This effectively reduces LDL cholesterol levels and reduces cardiovascular risks, such as heart attack and stroke. Simvastatin is a well-established, effective, and cost-efficient statin for lowering LDL cholesterol and reducing cardiovascular risk. However, it causes myopathy, rhabdomyolysis, myalgia, constipation, kidney failure, headache, abdominal pain, diarrhoea, nausea, and increased blood sugar levels with its use and higher doses of 80 mg/day. To address this, a liposomal simvastatin formulation with particle sizes of 150-250 nm was developed for intravenous administration. This formulation can potentially accumulate in the liver via passive targeting via the RES, thereby enhancing hepatic uptake and improving safety. The liposome was formulated using the thin-film hydration method and optimised using a central composite design. The optimized formulation's vesicle size was 204.66 ± 2.84 nm, with a PDI of 0.27 and a zeta potential of -58.11 mV, indicating uniform distribution and high stability. In-vitro drug release demonstrated controlled release of up to 92.46% over 60 h. The cellular toxicity assay showed that the optimized liposome was 10 times safer than pure simvastatin. In-vivo, the liposomal formulation significantly reduced lipid levels after administration of a 5 mg/kg dose in Triton X-100-induced hyperlipidemic rats, outperforming marketed formulations and standard drugs. Simvastatin-liposomes are safe, stable, and a more potent alternative to traditional oral simvastatin, offering improved liver targeting and a reduced toxicity profile.
Molecular biomedicineZhineng Wu, Jinghu Lou, Yi Cheng, Meng Li, Zengming Wang, Nan Liu, Xiang Gao, Aiping Zheng, Hui Zhang
mRNA vaccines have become a clinically validated vaccine platform, as demonstrated by the success of COVID-19 vaccines such as Comirnaty and Spikevax, owing to their rapid design, manufacturing scalability, and capacity to induce in situ antigen expression. A key factor underlying this success is the lipid nanoparticle (LNP) delivery system, which protects mRNA from degradation and promotes efficient cellular uptake and cytoplasmic delivery, thereby enabling the full potential of mRNA technology. The continued advancement of mRNA-LNP vaccines requires integrated optimization of mRNA design, LNP composition, and delivery strategies to achieve improved stability, efficient intracellular delivery, and balanced immune responses. Despite remarkable progress, challenges related to formulation stability, long-term storage stability, safety and reactogenicity concerns, and durability of immune protection continue to hinder the broader application of mRNA-LNP vaccine platforms. This review provides an integrated overview of recent advances in mRNA-LNP vaccines, covering mRNA molecular engineering, LNP composition and delivery mechanisms, immune responses, clinical progress, and current developmental challenges. Furthermore, emerging strategies, including thermostable formulations, next-generation LNPs with improved targeting capability, emerging RNA platforms, and artificial intelligence-assisted optimization of RNA sequences and lipid materials, are discussed. By summarizing current achievements and future opportunities, this review highlights key principles guiding the rational design of safer, more stable, and more precise mRNA-LNP vaccine platforms and provides insights into accelerating their clinical translation.
AAPS PharmSciTechMariame A Hassan, Bhanu Prakash Dongala, Annette DeSantiago, Ziyaur Rahman, Mansoor A Khan
Divalproex Sodium (DVS) is an antiepileptic agent with a narrow therapeutic window and a wide range of side effects. Its delayed-release forms demonstrated better tolerability in terms of gastrointestinal side effects. DVS has high sensitivity to temperature and humidity. Owing to a high frequency of daily administration, outpatients may keep their medication supply accessible in places that might not qualify for proper drug storage. In this study, five FDA-approved DVS delayed-release tablet products (A-E) were assessed for physical integrity, physicochemical changes and drug release pattern before and after repackaging in amber-colored closed pharmacy vials and storage at 30°C/75%RH. Initially, one product showed dissimilarity to the others (f1 = 19.6, f2 = 41.6). Upon storage, tablets showed signs of physical damage after 1 month. At 3 months, A, B and E tablets lost their integrity completely. Product C displayed high variability in acid (44.9 ± 31.5% drug release). Tablets that remained intact after storage failed the f1 and f2 tests. The images showed evidence of chemical changes in all products. The results indicated that repackaging and improper in-use keep could result in unpredictable drug release. It is debated that the total daily systemic bioavailability of DVS, rather than the peak-to-trough differences, is the primary determinant of seizure control. However, variability in drug release can result in gastric irritation, systemic side effects, drug intolerance and patients' noncompliance. This unnecessary burdening of the health care system can be avoided when revising dispensing and storage recommendations of DVS products.
ChemMedChemChristian S Carnero Canales, Ana Clara Lunardi Yagi, Túlio Custódio Reis, Jessica Ingrid Cazorla, Jade Rojas Villar, Marcia A Graminha, Roxana Yesenia Pastrana…
Malaria and leishmaniasis continue to impose a substantial health burden, while current therapeutic and diagnostic strategies remain limited by toxicity, prolonged regimens, drug resistance, and restricted field applicability. This review examines recent advances in peptide-enabled nanoplatforms for both diseases, with emphasis on intracellular targeting, drug delivery, and diagnostic innovation. Antimicrobial peptides, cell-penetrating peptides, peptoids, mimotopes, and peptide-functionalized nanocarriers have been explored to improve parasite targeting, intracellular delivery, pharmacokinetics, and antiparasitic efficacy. In parallel, peptide- and aptamer-based nanosensors have expanded the detection of clinically relevant biomarkers, including HRP2, pLDH, GP63, KMP-11, and kDNA, highlighting their potential for sensitive and modular diagnostics. Despite these advances, translation remains constrained by limited in vivo validation, insufficient pharmacokinetic standardization, incomplete toxicity profiling, poor batch reproducibility, protein corona-associated variability, and scarce validation under field-relevant conditions. Peptide-enabled nanoplatforms are therefore most likely to succeed when aligned with stage-specific parasite biology, realistic host cell-targeting requirements, and scalable implementation pathways in endemic settings.
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.VSohaila A Shoala, Haidy Abbas, Heba M Elbedaiwy, Marium M Shamaa, Manal A Elsheikh
Andrographolide (AG) has been reported for its anticancer activity. However, it is classified as a class IV in the biopharmaceutics classification system (BCS). Therefore, AG possesses low bioavailability due to its low solubility and permeability. In this study, hyaluronic acid-coated chitosan nanoparticles (Hyalo-CS-NPs) were formulated to enhance AG delivery and allow the active targeting of CD44 receptors overexpressed on breast cancer cells. Results showed optimized AG-Hyalo-CS-NPs with a size of 388.2 ± 1.41 nm, a zeta potential of -25.7 ± 1.58 mV, and an entrapment efficiency of 95.3%±1.01%. In vitro release profile revealed a sustained pH-responsive release from coated and uncoated CS-NPs with greater AG release under acidic conditions that mimic the tumor microenvironment. The MTT assay demonstrated the sharpest decline in the MCF-7 cell viability. Moreover, flow cytometry studies illustrated a significant apoptosis compared to uncoated nanoparticles and AG suspension. In addition, biochemical marker evaluation showed upregulating of the pro-apoptotic protein Bax and downregulating of Bcl-2, HER2, and Cyclin D1, confirming the underlying mechanism of the anticancer activity. Finally, confocal imaging showed higher intracellular uptake from coated and uncoated CS-NPs by 2.2-fold and 1.85-fold, respectively. In conclusion, AG-Hyalo-CS-NPs is a smart, targeted nanoplatform that improves AG anticancer efficacy in breast cancer management.
Archives of microbiologyHelal F Hetta, Fawaz E Alanazi, Hanan Alshareef, Ghareb M Soliman, Sultan A Almadi, Ageel F Aljuhani, Salwa Qasim Bukhari, Zinab Alatawi, Noura H Abd Ellah, Al…
Hypervirulent and multidrug-resistant Klebsiella pneumoniae represents a dual threat to global health, combining aggressive virulence with resistance to last-line antibiotics. Conventional therapies are failing, leaving an urgent need for disruptive approaches. Nanotechnology offers transformative solutions by enabling targeted drug delivery, dismantling biofilms, restoring antibiotic potency, and introducing novel modalities such as phage-nanoparticle hybrids and CRISPR-based nanoplatforms. This review synthesizes recent advances in metal-, polymer-, and lipid-based nanostructures designed to combat hvKp, highlighting mechanisms of action, synergistic combinations with antibiotics, and innovative theranostic systems. We also critically examine translational challenges, including reproducibility, safety, and regulatory uncertainty, while outlining future opportunities for precision nanomedicine through smart nanoplatforms, nano-enabled diagnostics, and AI-driven design. By integrating efficacy with safety and clinical feasibility, nanotechnology holds promise to reshape the therapeutic landscape for hvKp and MDR pathogens and contribute to broader strategies against antimicrobial resistance.
Journal of cancer research and clinical oncologyKhayrullina Aliya Khakimovna, Samadov Bakhodirjon, J Joseph Armstrong
This letter comments on a recent review of theranostic lipid nanocarriers for pancreatic ductal adenocarcinoma, identifying three areas of concern in the evidence base. First, the 211-item reference list contains multiple duplicated citations listed under separate numbers with identical content (for example, refs. 6/8, 9/21, 55/89, 106/117, 132/143), a recurring pattern suggesting that the bibliography was not fully verified before submission. Second, Table 6 cites reference markers "[639]" and "[640]" for the NanoSMART and NBTXR3 trials, numbers that exceed the 211-entry reference list and appear to be residual artifacts from a source document with a different numbering scheme. Third, the review reports that NC-6004 (a micellar cisplatin formulation) has completed a phase III trial in combination with gemcitabine but omits the trial's outcome, despite the review's broader argument for the translational viability of lipid- and micelle-based nanocarriers and its extended discussion of nab-paclitaxel as a successful precedent. Reporting this outcome, favorable or not, alongside existing precedents, would allow readers to weigh the review's central claim against the complete record of late-stage clinical testing. While the review offers a valuable catalogue of nanocarrier platforms and regulatory precedents, these issues warrant correction before the citation base is treated as fully reliable.