Aug 2026· Colloids and Surfaces B: Biointerfaces· Vol 268 Pt 2, pp.
116052
· 0 citations· 68 references
Medicine
TL;DR
Preliminary in vitro cytocompatibility under the tested conditions is supported, and the uniform particle size enabled comparison between single-particle moving-boundary kinetics and macroscopic release behavior, providing a physicochemical basis for pH-responsive oral delivery.
Abstract
The performance of targeted oral delivery systems for hydrophobic drugs like 5-aminosalicylic acid is limited by variable release kinetics and premature release in the upper gastrointestinal tract. To address this challenge, monodisperse 5-aminosalicylic acid nanocrystal-in-hydroxypropyl methylcellulose acetate succinate (5-ASA NCs@HPMCAS) composite microcapsules were prepared via microfluidic interfacial assembly and antisolvent precipitation. Droplet-templated solidification yielded microcapsules with an average diameter of 28.33 μm, a coefficient of variation < 3%, a drug loading of 20.4 wt% and an encapsulation efficiency of 83.3%. Driven by the pH-dependent transition of the HPMCAS shell, the microcapsules remained structurally intact under simulated gastric and proximal intestinal conditions (pH < 6.0) but underwent rapid interfacial erosion around pH 6.1. The model payload was released within approximately 3 min at pH 7.2 under quiescent in vitro conditions, while 5-ASA release reached 88.5% at pH 6.5 over 4 h. Ex vivo GI imaging of DiR-labeled microcapsules provided preliminary evidence of upper-GI retention and lower-GI localization after oral administration. Residual ethyl acetate was approximately 217 ppm, while dimethyl sulfoxide was below the assay's quantification range. A 24-hour Caco-2 assay showed cell viability above 90%, supporting preliminary in vitro cytocompatibility under the tested conditions. The uniform particle size also enabled comparison between single-particle moving-boundary kinetics and macroscopic release behavior, providing a physicochemical basis for pH-responsive oral delivery.
Poly(N-acryloyl glycine) (PNAG) bulk hydrogels are known to exhibit pH- and ion-responsive behavior. In this study, PNAG hydrogel particles were prepared by droplet-based microfluidics in combination with in situ photopolymerization. Rheological investigations led to the optimization of the PNAG gelation kinetics by the choice of photoinitiators, buffer media (pH 3, 7.4, or 9), and calcium ion (Ca2+) concentrations (none or 5 wt.% CaCl2). The microparticles demonstrated a strong swelling response, with a volume increase of over 5000 vol.% upon pH shifts. Rheology and multiple-quantum nuclear magnetic resonance (MQ-NMR) further revealed pronounced differences in network constraints and chain mobility between the investigated conditions. Via pH-induced swelling, model biopharmaceuticals such as glutathione (GSH) were loaded into the particles by soaking, followed by compound entrapment through Ca2+-induced network constriction, leading to high drug payloads >20 wt.%. Drug release studies revealed an initial burst release, followed by a remarkable prolonged diffusion-controlled release for about 2 weeks. As PNAG hydrogel particles demonstrated their potential for drug delivery, further studies could explore the tailoring of mesh sizes and broaden the spectrum of investigated biopharmaceuticals.
Yusuf Dursun, Burak Aydin, Bidit Lamsal et al.· Small· 0 citations
Conventional microsphere drug carriers for ulcerative colitis (UC) face challenges such as limited residence time, variable drug release, and an increased risk of systemic exposure and side effects. In this study, pH-sensitive, core–shell hydrogel microcapsules were designed and fabricated using a BUCHI B-390 microsphere preparation device via electrostatic interactions and hydrogen bonds. Olsalazine sodium was encapsulated in the microcapsules, allowing for pH-responsive drug release in colon tissue for UC treatment in mice. XRD studies demonstrated the amorphous state of the drug in the formulation. The preparation of SCO microcapsules was optimized based on the drug encapsulation efficiency and the drug loading capacity, with the S2C1O microcapsule having the highest drug encapsulation efficiency (59.2%) and drug loading capacity (21.3%), and the production yield was approximately 62.5%. The degradation experiment results indicated that the alginate/CMCS hydrogel shell has anti-resistant and colon-targeted properties, with minimal drug leakage under acidic conditions (0.1% release at 2 h, pH 1.2) and rapid, controlled release at colonic pH (7.4) (cumulative release of 68.7% at 12 h), protecting the drug from gastric degradation. An in vivo experiment suggested that treatment with these microcapsules in UC mice significantly reduced inflammatory markers (NF-κB p65 was reduced by 18.8% relative to the free drug group) and histological damage in UC models relative to free drug administration. The improved therapeutic efficacy is linked to precise localization in inflamed tissue, reducing systemic exposure and off-target effects. Overall, in vitro and in vivo studies demonstrated that this microcapsule system provides a promising alternative to existing UC drug delivery systems.
Qingqing Xue, Ying-Li Li, Qing Ao et al.· Gels· 0 citations
The emergence of antimicrobial resistance (AMR) necessitates the development of innovative delivery systems capable of maintaining enhanced therapeutic concentrations at the infection site. This study presents an innovative dual temperature and pH‐responsive nanogel system encapsulating poorly water‐soluble antibiotic fusidic acid, complexed with hydroxypropyl‐beta‐cyclodextrin (HPβCD) to improve solubility and facilitate controlled topical drug release. The fusidic acid‐HPβCD inclusion complex was synthesized to improve drug loading, and the resulting complex was encapsulated within nanogels (NGs). Fabricated via free radical polymerization, the optimized formulation (NIB‐7) demonstrated high drug entrapment efficiency (75.1% ± 1.7%) and exceptional pH responsiveness, exhibiting up to 600% ± 3.0% swelling at pH 7.4 compared to pH 1.2 (109.5% ± 3.0%). Characterization by Fourier Transform Infrared (FTIR) and Differential Scanning Calorimetry‐Thermogravimetric (DSC‐TGA) analysis demonstrated successful complexation and inclusion of the complex into a thermally stable nanogel matrix. A sustained release profile was demonstrated by in vitro release studies, with 76.5% ± 4.5% cumulative release observed over 48 h, prolonging the retention interval relative to the unencapsulated control. Kinetic modeling demonstrated that the drug release mechanism adheres to anomalous (non‐Fickian) transport (
n
= 0.68,
R
2
= 0.95), indicating that release is actively influenced by both fusidic acid diffusion and the reversible swelling/deswelling of the N‐Isopropylacrylamide‐Itaconic acid (NIPAM‐IA) polymer network in response to environmental stimuli (pH and temperature). This dual‐responsive system provides a promising foundation for localized and regulated antibiotic administration. The synergistic pairing of enhanced solubility by cyclodextrin complexation and the smart sustained release mechanism provided by thermo‐ and pH‐responsive nanogels offers significant possibilities to increase patient adherence and deal with antimicrobial resistance in the management of bacterial skin infections.
Azizullah Mukhtar, Waqas Ahmad, Hassan Ali et al.· Journal of Applied Polymer S...· 0 citations
Despite advances in chemotherapy, the clinical efficacy of docetaxel (Doc) in breast cancer treatment is limited by systemic toxicity and poor delivery efficiency. In this study, electrospun poly(lactic acid) (PLA):gelatin (Gel) core-shell nanofibers were developed as a dual drug delivery system for the co-delivery of Doc and heparin (HP). The core-shell architecture enabled the spatial compartmentalization of hydrophobic Doc within the PLA core and hydrophilic HP within the gelatin shell, allowing independent and controlled release profiles. Nanofibers containing 2, 3, and 5 wt% Doc in the core and corresponding amounts of HP in the shell were successfully fabricated. In vitro release studies performed at pH 3.0, 5.5, and 7.4 (37 °C) demonstrated a compartment-dependent release behavior, where HP exhibited rapid release (̴ 10 h), while Doc showed sustained release (̴ 80 h). These results indicate that the core-shell structure effectively regulates drug diffusion and enables distinct release kinetics for each therapeutic agent. Increased drug loading resulted in higher cumulative release for both agents. Cytotoxicity studies on MCF-7 breast cancer cells revealed that dual drug-loaded nanofibers (5 wt%, 2 mg) significantly reduced cell viability after 72 h, indicating enhanced in vitro antiproliferative activity. While Doc alone exhibited limited cytotoxic effect and HP showed negligible direct cytotoxicity, their combined delivery within the core-shell nanofiber system resulted in a markedly enhanced antiproliferative response. This enhanced effect indicates improved antiproliferative activity associated with dual-drug delivery through the core-shell nanofiber system. Overall, the developed PLA:Gel core-shell nanofibers represent a promising biomaterial-based platform for dual drug delivery of hydrophobic and hydrophilic agents, offering controlled release and promising in vitro antiproliferative activity.
S. C. Suner, A. Oral, Ayça Mehmetoğlu Al et al.· European journal of pharmace...· 0 citations
Novel anionic cross-linked hydrogel-based microparticles with controlled size, functionality, porosity, and morphology were synthesized via tailored precipitation polymerization of hydrophobic and hydrophilic monomers in the presence of dimethacrylate as a cross-linking agent. The resulting hydrogel microparticles (HG5), with a size of 250 ± 50 nm and a polydispersity index of 0.079, were readily dispersible in water and formed stable suspensions at physiological pH (7.2–7.4). Their physicochemical properties were comprehensively characterized using FT-IR, NMR, DLS, SAXS, TEM, and turbidimetry. HG5 efficiently incorporated albumin as a model antigen with a loading efficiency of 95%, forming stable hydrogel–protein complexes that maintained their hydrodynamic size and colloidal stability over one month of storage. Biological evaluation demonstrated low toxicity toward pseudonormal cell lines, with cell viability remaining above 50% at concentrations up to 5 mg/mL and no detectable apoptotic effects in HEK293 cells. Human peripheral blood mononuclear cells (PBMCs) were sensitive to HG5 exposure, exhibiting an IC50 of 0.52 mg/mL, while showing good hemocompatibility with hemolysis below 5%. HG5 significantly enhanced immunogenicity, increasing BSA-specific antibody levels by 1.9-fold compared to the immunization without adjuvant (p < 0.05). These findings demonstrate the potential of HG5 as a versatile platform for protein delivery and vaccine adjuvant development.
S. Ceylan, N. Mitina, N. Finiuk et al.· Gels· 0 citations
This research presents the development of a novel pH-sensitive PEG (HEMA-co-AA) graft copolymer hydrogel designed to provide controlled and protective delivery of acid-labile drugs, specifically Rabeprazole sodium. The hydrogel was synthesized using polyethylene glycol (PEG), 2-hydroxyethyl methacrylate (HEMA), acrylic acid (AA), with N,N'-methylene bisacrylamide (MBA) as a cross-linker and potassium persulfate (KPS) as an initiator. The hydrogel's structural integrity and formation were confirmed through Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and swelling studies. It is noteworthy that the hydrogel exhibits a different pH-dependent swelling behaviour, which expands under alkaline conditions and maintains its compact structure under acidic conditions. The content of acrylic acid contributed to the high-water retention and the swelling profile indicated that the product was suitable for the specific release of the drug at the site. The in-vitro release of rabeprazole sodium at acidic pH is very low, thus protecting rabeprazole sodium from premature degradation in the stomach; however, controlled release of rabeprazole sodium was achieved at intestinal pH via a non-Fickian diffusion mechanism (Korsmeyer-Peppas n = 0.40-0.62, Higuchi R² = 0.991-0.996) over 12 hours. Moreover, in-vivo acute toxicity studies indicated that the hydrogel is highly biocompatible, suggesting it is safe for use in future therapeutic applications. Overall, the PEG (HEMA-co-AA) hydrogel represents a versatile vehicle for the controlled and local administration of acid-labile pharmaceuticals, thereby promoting increased therapeutic efficacy.
U. Tulain, N. Malik, Alia Erum et al.· Journal of Pharmacy and Scie...· 0 citations
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