Pakistan journal of pharmaceutical sciencesSana Hanif, Farhang Hameed Awlqadr, Ijaz Ali, Saleha Yasir, Nariman Shahid, Umaira Rehman, Rouheena Shakir, Syed Hassan Murtaza, Muhammad Ali Syed
BACKGROUND: Sore throat ache is a discomforting condition for patients during the disease course while eating, drinking or swallowing. However, improved topical concentration of locally acting drugs can address this issue. OBJECTIVES: The goal of the current research was to formulate and evaluate the single-dose salivary pharmacokinetics of a chitosan (CT)-based mucoadhesive delivery system containing tibezonium iodide and lignocaine (LIG). METHODS: Mucoadhesive buccal gels were formulated using a homogenization technique and then subsequently characterized for physical, physicochemical and mucoadhesive properties. The ex vivo mucoadhesive studies were conducted on healthy New Zealand rabbits (aged 12-14 weeks and weight range in between 2.2-2.5 kg). RESULTS: Solid-state characterization revealed the absence of any unusual peaks in the physical mixture of the FTIR and DSC, whereas the unchanged physical form of drugs was confirmed through PXRD analysis. Formulations containing sodium alginate (SA) demonstrated greater swelling (15.39% in F4) but could not sustain drug release for up to 3 h at the polymer concentrations studied. Contrarily, poor mucoadhesive strength (MS) and mucoadhesive flow time (FT) were associated in formulations containing SA. Homogenization of CT and HPMC gels, when mixed at respective concentrations of 1.5% and 2% w/v, demonstrated sustained drug release over time, along with improved MS and FT values of 16.34 g and 142.20 min, respectively. Better salivary concentrations (Cmax) for LIG (5.14 µg/mL) and TIB (4.82 µg/mL) were observed at 2 and 3 h, respectively. CONCLUSION: Our study demonstrated higher Cmax concentrations of the locally acting drugs with single-dose mucoadhesive delivery in healthy volunteers, designed for sore throat, as a single-dose alternative to their respective conventional lozenges.
Pakistan journal of pharmaceutical sciencesGuangYan Wang, JingJing Shi, JieYin Liu, YuTing Zhai, Heng Su
BACKGROUND: Hypertension frequently coexists with coronary heart disease (CHD) and integrated management is essential to reduce cardiovascular and renal complications. OBJECTIVES: To evaluate the efficacy and safety of add-on sustained-release diltiazem capsules in patients with hypertension and CHD. METHODS: This retrospective cohort analysis included 302 consecutive patients with CHD treated at the Affiliated Hospital of Jiangnan University between May 2021 and May 2024. Patients were divided into a control group (n=158) receiving standard guideline-directed therapy and a diltiazem group (n=144) receiving add-on diltiazem sustained-release capsules. Propensity scores were used to match and balance baseline covariates to reduce selection bias. Following matching, intergroup comparisons for baseline characteristics, occurrence of cardiorenal composite endpoints, blood pressure, heart rate (HR) control during follow-up and adverse drug reactions were conducted. Multivariate regression analysis was used to determine predictors of cardiorenal endpoint events. RESULTS: After matching, baseline covariates were well-balanced between groups. During a median follow-up of 18 months, the cumulative incidence of cardiorenal composite endpoint events was lower in the diltiazem group than in controls (16.39% vs. 32.79%, P=0.002). Multivariate Cox analysis showed that diltiazem therapy was independently associated with a lower risk of composite outcomes (hazard ratio = 0.465, 95% CI: 0.284-0.760, P = 0.002). Patients receiving diltiazem also had a lower mean HR and higher achievement rates for HR control and combined blood pressure/HR targets (all P<0.05). The reduction in composite outcomes was primarily driven by fewer heart failure rehospitalizations. Drug-related adverse events were comparable between groups. CONCLUSION: Adding sustained-release diltiazem capsules to standard therapy is associated with a lower cardiorenal composite endpoint risk in patients with hypertension and CHD. The observed benefit was mainly driven by fewer heart failure rehospitalizations, alongwith improved control of blood pressure and heart rate. The renal findings should be considered exploratory because the number of renal events was limited.
Pakistan journal of pharmaceutical sciencesTao Wu, Xinlei Guan, Wenjuan He, Xiaoqiang Zhu, Liang Lei
BACKGROUND: Cholestatic liver injury (CLI) is a rapidly progressive liver disorder characterized by the accumulation of bile acids (BA). The therapeutic effects of current medicines used to treat CLI are unsatisfactory. OBJECTIVES: This study aimed to prepare galactosylated solid lipid nanoparticle (SLN) with swertiamarin (STM) by using a galactosylated lipid, N-hexadecyl lactobionamide (N-HLBA) and evaluate its anti-cholestasis effect in-vitro. METHODS: The galactosyl-lipid N-HLBA was prepared via the lactone form intermediates of lactobionic acid and synthesized by anchoring galactose to hexadecylamine lipid. The STM-loaded galactosylated SLN (STM-GalSLN) was successfully prepared by a melt-emulsification-ultrasound method. The prescription was optimized by orthogonal test. The morphology was observed by transmission electron microscope. The particle size and zeta potential were determined by laser granularity equipment. The encapsulation efficiency (EE) and drug loading capacity (DL) were determined by ultrafiltration, centrifugation and HPLC method. RESULTS: The optimized prescription was as follows: 50 mg of STM, 20 mg of N-HLBA, 500 mg of glyceryl behenate, 400 mg of soybean lecithin, 200 mg of poloxamer188 and 500 mg of Tween 80. The STM-GalSLN was spherical in shape and its particle size, zeta potential, EE and DL were 164.40 ±4.68 nm, -14.53 ±3.20 mV, 82.41 ±2.88 % and 0.32 ±0.02 %, respectively, and the EE of STM-GalSLN did not change significantly over 30 days at 4°C. Furthermore, STM-GalSLN alleviated cholestatic liver injury (CLI) in a concentration-dependent manner in-vitro. CONCLUSION: The findings from this study indicated that the melt-emulsification-ultrasound method was rational and reliable, which provided an experimental basis for developing a new nano preparation of STM for CLI.
This work reports the development and systematic evaluation of a carboxymethyl cellulose (CMC)-based nanocarrier system co-loaded with cerium oxide (CeO2) and carbon quantum dots (CQDs) for pH-responsive delivery of quercetin (QC) and in vitro evaluation in lung cancer cells. The nanocarriers were prepared using a water-in-oil-in-water (W/O/W) double emulsion approach, yielding spherical particles with an average size of approximately 134 nm and a high positive surface charge (+66 mV), indicative of favourable colloidal stability. FESEM analysis confirmed a uniform morphology and compact internal structure. The incorporation of CeO2 appears to reinforce the polymer matrix, contributing to improved drug encapsulation. The optimized formulation exhibited high encapsulation efficiency (88%) and drug loading capacity (47%), outperforming CeO2-free systems. In vitro release studies demonstrated a clear pH-dependent biphasic behaviour, with significantly faster release under pH 5.4 compared to physiological pH (7.4), reaching 98% and 58% after 96 h, respectively. Drug release followed the Higuchi model, suggesting diffusion-controlled kinetics, while the Korsmeyer-Peppas model indicated a non-Fickian mechanism. An AI-guided nonlinear modelling workflow was used to extract interpretable kinetic descriptors directly from experimental release data. Biological evaluation revealed enhanced anticancer activity against A549 cells, with viability reduced to 49.1%, while maintaining high biocompatibility towards L929 cells.
Drug deliveryGabriela Koutná, Jan Kotouček, Jan Macků, Kateřina Kubová, Martina Urbanová, Larisa Janisová, Ivana Šeděnková, Jan Muselík, Jakub Vysloužil, Josef Mašek, Elišk…
Self-microemulsifying drug delivery systems (SMEDDS) containing volatile phytotherapeutics such as thymol (T), carvacrol (C), and eugenol (E) present significant formulation challenges, even when solidified. Their instability and interactions with coatings often hinder intestinal delivery. To address these limitations, we developed solid SMEDDS consisting of pellets (microcrystalline cellulose/magnesium aluminometasilicate/chitosan) and enteric capsules (CEC) for enhanced intestinal delivery. Based on solubility and pseudo-ternary phase diagrams, SMEDDS formulations (SES1-3) differing in component ratios (glycerol monooleate/caprylocaproyl macrogol-8 glycerides/diethylene glycol monoethyl ether) with 5% w/w of each drug were identified, demonstrating nano-scale droplet sizes (PDI <0.4) and showing no phase separation over 6 months. Thermodynamic stability and liquid-state NMR revealed particle size variations with preserved structural integrity. The lead formulation SES1 exhibited superior ex-vivo intestinal permeation (T-SES1). CECs filled with T-, C-, and E-loaded SES1 pellets, respectively, prepared via extrusion/spheronization, exhibited in-vitro gastro-resistant release, and achieved > 85% drug release within 120 min after a pH change to 6.8 during a one-year stability study (25 °C; 60% RH). FTIR-ATR analysis of the CEC internal surface confirmed the temperature-dependent restructuring of hypromellose and E sorption, a phenomenon not observed with C or T, which is likely attributable to physicochemical distinctions. Oral administration of CEC with T-SES1-pellets (0.5 mg/kg) in piglets demonstrated a delayed peak plasma concentration (Cmax 11.67 ng/mL at 9 h) and sustained systemic exposure (AUC 119.8 ng·h/mL). These in-vivo findings substantiate the gastro-protective effect and enhanced intestinal absorption, positioning the pellet/CEC system as a promising strategy for the application of volatile phytotherapeutics in current pharmacotherapy.
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.VJuan Ma
The growing demand for subcutaneous (SC) self-administration of biotherapeutics, driven by the rising prevalence of chronic diseases and healthcare cost-containment pressures, has accelerated the development of high-concentration formulations (HCFs). However, protein concentrations exceeding 100 mg/mL introduce significant challenges, including solubility limitations, high viscosity, aggregation propensity, injectability constraints, and manufacturing complexities. This review systematically examines the primary obstacles in HCF development and highlights recent advances in formulation and process technologies. Key strategies include: (i) excipient-based viscosity reducers; (ii) hyaluronidase-enabled large-volume SC delivery; (iii) lyophilization for decoupling manufacturing from final concentration; (iv) spray drying platforms including SnapShot™ and XeriJect®; (v) electrostatic spray drying (Elektroject™ Hypercon™); (vi) Microglassification™ dehydration technology; and (vii) protein crystallization (Crystalomics®). Collectively, these innovations are reshaping the landscape of high-concentration biologic drug products, enabling the transition from intravenous to subcutaneous administration for a broader range of therapeutics. This review serves as a strategic guide for formulation scientists and drug developers engaged in next-generation subcutaneous biologics.
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.VXiaoyang Li, Xiaodan Wang, Yan Ming, Rongtao Li, Yun Yang, Jing Wang, Baiyu Chang, Qing Zhang, Jingling Tang, Jiaxin Liu, Hongyu Ji, Congcong Lin
Chronic wounds pose notable clinical challenges due to persistent infection, inflammation, and impaired tissue regeneration. We designed a multi-functional microneedle patch (MR-NPs-MNs) comprising chitosan-based microneedles encapsulating PLGA nanoparticles co-loaded with mupirocin and L-arginine. As a key component, L-arginine significantly enhances anti-inflammatory effects by reducing pro-inflammatory cytokines and effectively promotes tissue repair by regulating oxidative stress and facilitating angiogenesis. The PLGA nanoparticles MR-NPs exhibited stable physical properties (181.7 ± 5.875 nm particle size, 22.4 ± 0.529 mV zeta potential) and were incorporated into microneedles capable of withstanding 40.38 N compression. Notably, MR-NPs-MNs outperformed conventional mupirocin ointment, achieving a 99.82 ± 0.15% antibacterial rate (vs. 90.69 ± 1.11% for the ointment), superior biofilm inhibition (96.82 ± 0.83% and 77.8 ± 5.32%), and enhanced transdermal drug delivery. In vitro, MR-NPs-MNs increased NO production, reduced TNF-α, IL-6 and ROS levels, and promoted wound healing. In diabetic wound models, MR-NPs-MNs increased the healing rate by 1.54-fold, significantly reduced bacterial counts (P < 0.01) by day 9, and improved key healing parameters including collagen matrix reorganization, robust neovascularization, and functional tissue formation. With its biocompatible components, this system provides a potential local therapeutic platform for infected diabetic wound treatment.
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.VMaria Antonia S de Albuquerque, Douglas F de Albuquerque
Mathematical models for drug release from polymeric nanocapsules have traditionally relied on Noyes-Whitney-based first-order kinetics, which implicitly predict faster release for drugs exhibiting higher solubility in the oily core. This prediction is inconsistent with numerous experimental observations in which more lipophilic compounds are released more slowly. To address this apparent paradox, a partition-controlled kinetic framework is derived in which the effective release rate scales inversely with oily-core solubility. The resulting model, [Formula: see text] introduces a dimensionless correction factor α and a reference solubility S0, yielding a dimensionally consistent formulation while preserving the mechanistic inverse-solubility dependence predicted by partition equilibrium arguments. A re-analysis of the previously published nanocapsule model reveals a dimensional inconsistency and a tabulation error affecting the reported kinetic parameters. After correction, the published adapalene data are found to be consistent with the proposed inverse-solubility scaling. The model is further evaluated using four release datasets (adapalene in two oily cores, capsaicin, and dihydrocapsaicin), yielding R2 values between 0.925 and 0.969 with Cmax fixed at the final experimental value. These results support partition-controlled release as a physically plausible and dimensionally consistent framework for describing drug release from polymeric nanocapsules.
Human vaccines & immunotherapeuticsVivek Shinde, Wayne Woo, Anthony M Marchese, Susan Neal, Joyce S Plested, Timothy S Vincent, Mingzhu Zhu, Shane Cloney-Clark, Iksung Cho, Louis Fries, Raburn M…
Based on viral evolution, increases in seasonal infections, and facilitation of delivery, an annual combination vaccine simultaneously targeting influenza and SARS-CoV-2 would benefit public health. The safety and immunogenicity of a COVID-19-Influenza Combination nanoparticle vaccine (CIC) containing SARS-CoV-2 recombinant spike (rS) to the ancestral strain (Wuhan) and quadrivalent influenza hemagglutinin with a Matrix-M® saponin-based adjuvant were evaluated in a phase 1/2 blinded, randomized trial. The safety, tolerability, and immunogenicity of a CIC two-dose series were assessed and compared with standalone quadrivalent influenza (qNIV) and monovalent COVID-19 (NVX-CoV2373) vaccines. Reactogenicity events, unsolicited adverse events (AEs), antiviral microneutralization responses, hemagglutination-inhibition antibody titers, anti-rS protein immunoglobulin G, and human angiotensin-converting enzyme 2 receptor binding inhibition antibody responses for SARS-CoV-2 were measured. All participants had been previously vaccinated against ancestral SARS-CoV-2. From September 8, 2021, to April 22, 2022, 642 participants were enrolled and randomized into the study; 637 received at least one vaccination. After each dose, CIC formulations induced antibody responses against homologous and heterologous influenza and SARS-CoV-2 strains that were comparable with the references. The CIC vaccine group had similar incidence of solicited and unsolicited AEs as the qNIV and NVX-CoV2373 reference groups. Severe unsolicited AEs only occurred in the CIC group but were infrequent and not considered related to the study vaccine. Overall, CIC formulations displayed reference-comparable safety and immunogenicity and provided data for statistical modeling analyses to optimize influenza hemagglutinin and SARS-CoV-2 rS antigen concentrations for use in phase 2 clinical trials investigating CIC.
Drug deliveryYanping Yin, Lulu Zhang, Yanli Yin, Jinyi Zhao, Rui Gong, Xuan Zhou, Haiyue Zhang, Fei Mu, Jingwen Wang
Sepsis-induced liver injury (SILI) is an important cause of death in intensive care patients, which seriously affects clinical prognosis. Wedelolactone (WEL) exhibits hepatoprotective properties, however, its clinical application is constrained by its poor solubility and insufficient targeting ability. Therefore, in this study, an innovative exosome (Exo)-based drug delivery system loaded with WEL (Exo@WEL) was constructed. The aim was to enhance the liver-targeting efficacy and therapeutic performance of WEL. Exo were extracted from the mice macrophages cell line RAW264.7 by differential centrifugation, and WEL was successfully loaded using ultrasonic incubation. Exo@WEL was characterized by TEM, particle size analysis, and NTA, confirming its structural suitability as an exogenous agent. DiR labeling revealed that Exo@WEL had a significantly enhanced liver-targeting ability compared to WEL. Safety was confirmed by HE staining test. In the SILI models, Exo@WEL showed better hepatoprotection over WEL. Beyond entinfinmtory actvity menifested y decreased ro infammatory rokines, Exo@WEL reinforced antioxidant function and efectively restained feroptosis. Importantly, pharmacological inhibition of ML385, a selective Nrf2 inhibitor, confirmed the critical regulatory role of the Nrf2 pathway in mediating these multifaceted liver protective effects. This study pioneered the development of a targeted Exo-based nanoplatform (Exo@WEL) for SILI therapy. The mechanism study has revealed a potential therapeutic strategy for inhibiting oxidative stress and ferroptosis by regulating the Nrf2/SLC7A11/GPX4 axis. This preparation provides a novel nanotherapeutic strategy that combines high efficiency and safety for the treatment of SILI. These findings also lay a theoretical foundation for the clinical translation of Exo drug delivery systems.
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.VMohamad Hamdi Zainal-Abidin, Maan Hayyan, Gek Cheng Ngoh, Won Fen Wong, Chung Yeng Looi, Mohd Basyaruddin Abdul Rahman, Norazlinaliza Salim, Tan Ee Fei
The future of graphene as a drug nano-carrier lies in nanotechnolgy where it can be tailor-made to favor the cellular biological environment. Therefore, an innovative route was implemented to improve the biocompatibility of graphene using binary and ternary sugar-based deep eutectic systems (DESs) as green functionalizing agents with composition of choline chloride (ChCl):glucose (2:1), ChCl:fructose (2:1), ChCl:fructose:water (5:2:5), and ChCl:glucose:water (5:2:5). The changes in physicochemical properties of sugar-based DES-functionalized graphene were observed via FESEM, FTIR, BET, XRD, and Raman spectroscopy, testifying the addition of DES-functional groups. The biocompatibility of graphene was significantly improved post functionalization with sugar-based ternary DES compared to sugar-based binary DES as validated in biological assays. The ternary DES-functionalized graphene demonstrated higher doxorubicin (DOX) loading capacity as compared to the binary DES-functionalized graphene. To gain molecular-level insights, computational simulations via quantum chemical calculations were performed to elucidate the interactions between graphene, DES components, and DOX. After DOX loading, the graphene exhibited damaging impacts against cancerous cells through the intracellular ROS production and cell cycle disruption phenomena. Real-time cell growth analysis was further investigated to confirm the cytotoxicity kinetic response of DOX loaded-Gr against cancerous cells over time. The results of this cellular kinetic response were in accordance with the DOX loading capacity data. Sugar-based ternary DESs, ChCl:glucose:water and ChCl:fructose:water, were the most promising functionalizing agents for nano-drug carriers, owing to their lower cytotoxicity, higher drug loading capacity, and significant inhibition of the cancer cell growth profile.
Drug deliveryJoanna Sobocińska, Chun Yuen Jerry Wong, Emre Gezer, Hui Xin Ong, Youssef Daali, Véronique Serre-Beinier, Daniela Traini, Muriel Cuendet
Resveratrol is a polyphenolic compound with therapeutic potential for pulmonary diseases, yet its use is limited mostly due to low oral bioavailability. Inhalable powder formulations are a promising strategy to help overcome those challenges. Here, we report the development and physicochemical characterization of a spray-dried resveratrol formulation suitable for pulmonary delivery. The pharmacokinetic profile and in vivo toxicity were then assessed. Particle size, interparticle cohesion, morphology, uptake, and stability of the formulation were evaluated. Intratracheal administration was then performed in A/J mice and pulmonary distribution was compared to a micronized resveratrol formulation. Lung and plasma concentrations were quantified by LC-MS/MS at 5-70 min postadministration, followed by long-term toxicity evaluation. The spray-drying process produced resveratrol with improved lung exposure while preserving properties essential for pulmonary delivery. In vivo, the spray-dried formulation achieved improved pulmonary and lower systemic distribution compared to the micronized form, increasing the lung to plasma AUC ratio from 77 to 282. Moreover, a greater number of mice had detectable concentrations of resveratrol in the lungs following spray-dried administration (62.5% vs 37.5% for micronized). The long-term intratracheal administration of spray-dried resveratrol (1 mg, 3× per week for 12 weeks) was well tolerated, with no clinical, biochemical, or histopathological signs of toxicity. Altogether, the spray-dried formulation of resveratrol could be efficiently delivered to the lungs and displayed an excellent safety profile, supporting its future investigation in respiratory disease models.
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.VTiandian Wang, Anuj A Biswas, Feng Zhang, Rongjin Sun, Ming Hu
With annual overdose deaths in the United States over 1 million, medication-assisted treatment with buprenorphine (BUP) remains the first-line, gold-standard therapy for opioid use disorder (OUD). Because OUD is a chronic, relapsing condition that requires long-term pharmacotherapy, long acting injectables (LAI) and implantable formulations offer important advantages over daily formulations for maintenance treatment. By comparing transmucosal BUP and LAI formulations' systemic exposure profiles and μ-opioid receptor (MOR) occupancy, converging data demonstrate that higher and more sustained BUP exposure with low variability is required to fully suppress withdrawal, cravings, and illicit opioid use. These findings indicated that currently marketed formulations may not adequately address the clinical challenges associated in the fentanyl/polysubstance era. Accordingly, this rationale-based review proposes a mechanistic framework supporting the development of next-generation BUP-PLGA solid biodegradable implants to maintain a conservative therapeutic benchmark (e.g. Css ≥ 5 ng/mL) for extended durations (e.g. 3-6 months) with low variability (e.g. no large burst release, major lag phase or phase inversion). However, progress in implant development has been hindered by limited mechanistic understanding of drug release. In PLGA-BUP systems, poor IVIVC is largely driven by the low and pH-dependent solubility of BUP, which can make dissolution rate-limiting in vivo and interact with the evolving PLGA acidic microenvironment (acidification, porosity formation, and autocatalytic degradation). Future research should be prioritized to determine directly whether polymer erosion coincides with drug release in PLGA depots, or whether residual, poorly soluble BUP persists locally and releases under dissolution-limited kinetics. Clarifying these mechanisms is not only essential to fulfill the regulatory and translational expectations of the FDA and NIDA, but also to deepen mechanistic understanding and accelerate the rational development of LAI formulations for poorly soluble drug.
Advanced drug delivery reviewsMainak Banerjee, Alexandre Detappe, Twan Lammers
Targeted protein degraders (TPDs), including proteolysis-targeting chimeras (PROTAC) and molecular glue degraders (MGD), are among the most promising small-molecule-based drug treatments in oncology. The May 2026 U.S. Food and Drug Administration (FDA) approval of vepdegestrant provides a regulatory milestone for heterobifunctional protein degradation and for PROTAC therapeutics. First-generation TPDs were developed for oral delivery; however, the intrinsic physicochemical properties of TPDs impose constraints on their oral bioavailability, systemic exposure, target-site accumulation, and therapeutic efficacy. As the field transitions toward a second wave of TPD development, nanoparticle-based targeted protein degraders (nano-TPD) are gaining momentum for broadening the therapeutic landscape of protein degradation. In this context, drug delivery systems offer opportunities to overcome key translational barriers by improving pharmacokinetics, tissue distribution, target site localization, cellular uptake, and therapeutic index. Here, we provide an overview of TPD discovery, from early laboratory to (pre-) clinical progress, discuss translational challenges, and suggest advanced drug delivery solutions to help realize the full potential of TPD therapies.
Advanced drug delivery reviewsPeixin Liu, Tianyi Ma, Quanyin Hu
Lysosome-targeting degraders (LYTADs) are bifunctional molecules that harness lysosomes to degrade pathogenic proteins. This breakthrough technology addresses a gap in cell membrane- and extracellular protein-targeted degradation technologies. Together with proteolysis-targeting chimeras, LYTADs have driven the development and application of targeted protein degradation (TPD) in biomedicine and other fields, making it one of the most prominent chemical biology technologies of the 21st century. Currently, LYTAD technology has been extensively researched and expanded, demonstrating its ability to degrade a variety of pathogenic proteins across cells, tissues, and diseases, and is not limited to TPD. LYTADs are now in the critical stage of translating their concepts into clinically validated drugs. Many emerging limitations and challenges cannot be addressed through structural design and optimization alone. With the increasing demand for accelerated clinical translation, delivery systems are being used to improve the physicochemical properties of LYTAD molecules in both in vivo and in vitro settings. By combining delivery system design strategies with LYTAD design, or by harnessing delivery systems to deliver LYTADs, the targeting capabilities, therapeutic effects, and biosafety of LYTADs can be enhanced. This integration of delivery systems and LYTADs brings new breakthroughs and opportunities to the field of TPD. In this review, we summarize recent advances in LYTAD delivery systems, focusing on design strategies and biomedical applications. We will also discuss the current challenges and envision future development opportunities of this technology in the biomedical field.
Biochemical and biophysical research communicationsZeinab Koolabadi, Niloofar Taghipour, Maryam Rouhani, Masoud Soleimani, Saeed Heidari Keshel, Azam Rahimi, Bahareh Pourjabbar, Farzaneh Saeedi Landi
Diabetic foot ulcers represent chronic and often non-healing wounds. Their treatment is particularly challenging due to persistent inflammation and infection, necessitating the exploration of innovative strategies for more effective therapeutic approaches. This study aimed to develop a biodegradable extracellular matrix-mimicking wound dressing with anti-inflammatory properties designed to control inflammation and support cell proliferation and migration in the wound area. The anti-inflammatory drug prostaglandin J2 (15d-PGJ2) was encapsulated in PLGA nanoparticles (NPs). The average hydrodynamic size and zeta potential of 15d-PGJ2-loaded NPs were 261.6 nm and -14.3 mV, respectively, with a polydispersity index below 0.2. The entrapment efficiency and drug loading were 96.7% and 18.5%, respectively, with 50% of the drug released within 240 min. Cellular studies, including MTT assays and scratch tests, were performed to evaluate drug toxicity and determine the safe dose of NPs. Porcine small intestinal submucosa (SIS) sheets were cross-linked with EDC/NHS and integrated with NPs. The modified scaffolds were subjected to in vitro characterization, including FTIR analysis, enzymatic degradation, swelling behavior, contact angle measurements, mechanical evaluation, and cell adhesion studies. They demonstrated a hydrophilic surface with suitable water adsorption capacity, a low degradation rate, enhanced mechanical strength, and effective interaction with fibroblast cells. The EDC-crosslinked SIS scaffold carrying anti-inflammatory NPs exhibited promising characteristics based on its physicochemical and biological properties. Thus, it can be considered a suitable option for diabetic wound healing.
Food research international (Ottawa, Ont.)Yiran Qian, Xiaoxi Chang, Chenyan Lv, Jiachen Zang, Guanghua Zhao, Tuo Zhang
Poor gastrointestinal stability and inefficient intestinal absorption remain major bottlenecks limiting the nutritional efficacy of food bioactives. Although protein-based carriers are widely investigated because of their edible origin, biodegradability, structural diversity, and tunable assembly behavior, many studies still emphasize material-level parameters rather than bioavailability-relevant performance. This review re-examines protein-based oral delivery systems through a gastrointestinal barrier-oriented framework. Representative carriers, including plant prolamins, legume globulins, oilseed and tuber proteins, albumins, milk proteins, fibrous proteins, ferritin cages, virus-like particles, elastin-like polypeptides, and silk fibroin, are discussed according to their structural features, assembly behavior, digestion fate, and delivery functions. Particular attention is given to how protein architectures can be engineered to improve gastric protection, protease resistance, mucus penetration, epithelial interaction, regional retention, and controlled release. Rather than treating protein source as the primary determinant of delivery performance, this review highlights carrier-barrier compatibility as the central design principle. Current evidence suggests that effective systems increasingly require integrated functions, including colloidal stability, food-grade manufacturability, safety, sensory compatibility, and measurable bioavailability enhancement. Future development should move beyond proof-of-concept encapsulation toward standardized digestion-absorption models, quantitative in vivo evaluation, and scalable processing strategies suitable for functional foods and dietary supplements.
Food research international (Ottawa, Ont.)Xueli Liu, Xiaoxue Wang, Junxia Xia, Bing Qi, Kuizhang Yao, Dayong Zhou, Liang Song
The entrapment of lipophilic bioactives within hydrophilic polymer matrices presents physical challenges regarding phase separation and uncontrolled release. This study evaluates a strategy based on tuning lipid phase behavior to modulate the microstructural evolution of α-tocopherol-loaded nanoemulsions and derived pullulan films. A 40% coconut oil proportion induced a transition from a disordered supercooled liquid to an ordered viscoelastic fluid. This state facilitated the formation of stable nanodroplets with a mean diameter of 18.59 nm and a polydispersity index of 0.24 by reducing the interfacial tension to 5.07 mN·m-1 and the critical micelle concentration to 0.01 g·L-1. Conversely, a 60% coconut oil proportion caused microstructural crowding and interfacial bridging. This highly homogeneous architecture was preserved within the solid film, yielding a tensile strength of 26.51 MPa, an elongation at break of 15.14%, and reduced permeabilities for oxygen (0.14 × 10-4 g·m-1·s-1) and water vapor (1.04 × 10-13 kg·m-1·s-1·Pa-1). Kinetic modeling confirmed a quasi-Fickian diffusion profile in which the embedded nanodomains functioned as steric obstacles. This tortuous diffusion path restricted solute mobility, suppressing the initial release and achieving an 88.88% retention of tocopherol activity. Application on walnut kernels demonstrated preservation efficacy, evidenced by a 39.94% reduction in peroxide value and a 38.56% decrease in thiobarbituric acid reactive substances compared to the control group. Regulating internal lipid phase behavior provides a predictable microstructural framework for developing active packaging systems to extend the shelf life of lipid-rich foods.
Food research international (Ottawa, Ont.)Yanpei Huang, Conghui Lang, Fei Ren, Jinsheng Fu, Shengmin Liu, Chuang Zhang, Kai Shan, Chunbao Li, Wenxue Chen, Ming Zhang, Qiujin Zhu, Haiming Chen
We developed a pH/polyphenol-controlled dual-response intelligent hydrogel absorbent pad based on methylcellulose and sodium alginate (MC-SA). The hydrogel was incorporated with composite particles consisting of anthocyanins encapsulated in metal-organic frameworks (MOFs). Synergistic interactions between anthocyanins and MOFs enhanced the pad's water absorption (511.4%) and retention capacity (88.9%), swelling properties, and thermal stability. The pad possessed antimicrobial (TVC < 6 log(CFU)) and antioxidant activity and thereby could suppress microbial growth and lipid/protein oxidation (TBARS: 0.76 mg MDA/kg; total sulfhydryl content: 46.25 μmol/g) in fresh pork during 9 days of storage at 4 °C. Furthermore, with their pH-responsive color change and controlled release properties, the incorporated anthocyanins enabled real-time visual monitoring of pork freshness and preservation efficacy. Among all hydrogel pads, the MC-SA-Ant@Fe-MOFs pad showed the most optimal preservation performance and was able to extend pork shelf life by 2-4 days. This pad also exhibited excellent biocompatibility and soil degradability. Overall, this study presents a pH/polyphenol-controlled dual-responsive smart hydrogel absorbent pad that can serve as both a preservative material and a freshness indicator.
Food research international (Ottawa, Ont.)Youngkyoung Jeong, Areum Han, Yoon Hyuk Chang
The objective of this study was to evaluate the physicochemical, structural, and in vitro release properties of low methoxyl pectin (LMP)-based particle gel beads incorporating apigenin-loaded porous starch (APS) as a colon-targeted delivery system. LMP-based particle gel beads incorporating APS were prepared as a colon-targeted delivery system for apigenin (AP). Porous starch (PS) was prepared using α-amylase and amyloglucosidase for 12 h of enzymatic treatment. AP was then adsorbed onto PS to prepare APS. APS was then incorporated into an additional LMP-based hydrogel bead layer with different concentrations of CaCl2 (2%, 3%, and 4%) to fabricate particle gel beads. XRD analysis revealed that APS was successfully incorporated into LMP-based particle gel beads. According to FT-IR analysis, AP was adsorbed onto PS by hydrogen bonding, and LMP-based particle gel beads were prepared via ionic crosslinking between LMP and CaCl2. FE-SEM images revealed that the surface of the particle gel beads became smoother, and their internal structure was more compact as concentrations of CaCl2 increased. The encapsulation efficiency of the particle gel beads increased from 87.95% to 93.54%, with an increase in CaCl2 concentration from 2% to 4%, respectively. In vitro release study indicated that LMP-based particle gel beads maintained better stability than APS throughout the simulated oral, gastric, and intestinal conditions, effectively delivering AP to the colon. Within simulated colon conditions, increased CaCl2 concentration delayed AP release, demonstrating enhanced controlled delivery. Results from the storage stability evaluation additionally indicated that LMP-based particle gel beads provided higher stability for apigenin than APS.