pH-responsive microneedle patches based on poly(dextran-co-methacrylic acid) hydrogels for controlled drug release.

PEG-g-(HEMA-co-AA) pH-responsive graft copolymer: A promising approach for the controlled oral delivery of acid-labile rabeprazole sodium.

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.

A microenvironment-responsive microsphere-PLGA-PEG-PLGA hydrogel for sustained and coordinated co-delivery of celecoxib and ropivacaine in osteoarthritis therapy.

Dual-Stimuli Responsive Poly(N-acryloyl glycine) Microgels: Investigation of Network Structures and Application for Loading and Release of Biologics.

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.

Preparation and Sustained Drug Release Study of Interpenetrating Network PNIPAm / SA (Ca 2+ ) Hydrogels

A polyaspartic acid derivative was synthesized as a crosslinking agent (AEA‐PSI), and its structure was analyzed using proton nuclear magnetic resonance ( 1 H NMR) and Fourier transform infrared spectroscopy (FTIR). A temperature‐ and pH‐responsive hydrogel based on sodium alginate (SA) and N ‐isopropylacrylamide (NIPAm) was synthesized and characterized by FTIR, scanning electron microscopy (SEM), X‐ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), and mercury intrusion porosimetry (MIP) to confirm its structure and thermal stability. The formulation was systematically optimized by varying SA content, NIPAm concentration, and crosslinker dosage, yielding hydrogels with tunable swelling capacity and network structure. Incorporating AEA‐PSI refined the three‐dimensional network without compromising its temperature‐ and pH‐responsive behavior. This tailored structure facilitated sustained drug release: the optimized hydrogel exhibited significantly higher 5‐fluorouracil (5‐FU) release in simulated intestinal fluid (SIF, pH = 7.4, 90.19%) compared to simulated gastric fluid (SGF, pH = 1.2), with release kinetics following the Ritger–Peppas model. Furthermore, the hydrogel demonstrated superior biodegradability in intestinal fluid and lysozyme solution, a functional advantage rarely achieved in conventional alginate‐based hydrogels. This work presents a successful valorization of natural and synthetic polymers into a tunable and biocompatible drug‐delivery platform, achieving a synergistic combination of responsiveness, sustained release, and biodegradability for the treatment of small intestine–related diseases.

Development of stimuli-responsive polymeric hydrogels and their applications

Electro-responsive nanocomposite hydrogels based on gelatin, partially neutralized acrylic acid (PAAc), and acid-functionalized multiwalled carbon nanotubes (MWCNT-COOH) were developed and evaluated as potential smart drug delivery systems. The successful functionalization of pristine MWCNTs was confirmed by the shift in characteristic X-ray diffraction (XRD) peaks, while the presence of MWCNT-COOH peaks in the nanocomposite hydrogel verified their effective incorporation into the polymer matrix. Scanning electron microscopy (SEM) revealed distinct morphological changes following acid functionalization and demonstrated the uniform dispersion of MWCNT-COOH within the hydrogel network, resulting in a smooth and homogeneous surface. Swelling studies showed that increasing MWCNT-COOH content reduced the swelling percentage in the absence of an electric field, whereas the application of a 10 V electric field significantly enhanced swelling, confirming the electro-responsive nature of the hydrogels. In vitro hemolysis assays indicated excellent blood compatibility, highlighting their suitability for biomedical applications. The electro-responsive release of vitamin B12 was strongly influenced by the ionic strength of the release medium, applied voltage, and MWCNT-COOH concentration. Furthermore, drug release behavior was systematically optimized using response surface methodology based on a central composite design. Overall, the developed Gelatin-g-PAAc/MWCNT-COOH nanocomposite hydrogels exhibit favorable structural, swelling, biocompatible, and electro-responsive characteristics, making them promising candidates for the design of advanced electrically controlled drug delivery systems.

Stimuli-Responsive Biopolymer Carboxymethyl Tamarind-Based Hydrogel Composite Impregnated With IONPs for Sustained Administration of Levofloxacin.

pH-sensitive polymeric hydrogels are considered promising candidates for oral drug delivery because they can respond to changes in the surrounding environment or adapt to the biological environment. In the present study, novel hydrogel composites were developed via free radical polymerization using biogenically (Citrus limetta peel extract) synthesized iron oxide nanoparticles (IONPs) as fillers, carboxymethyl tamarind kernel gum as a biopolymer, and poly(acrylamide) to form the polymeric network of CMTG-PAM-IONPs hydrogel composite for levofloxacin delivery. The prepared hydrogel composites were characterized, and swelling studies were carried out to evaluate the influence of IONPs on the swelling behavior of the hydrogels. The results showed that the effect of IONPs on swelling became more noticeable when the nanoparticle concentration in the hydrogel formulation was increased up to approximately 0.02 g. In addition, the gel content and porosity of the hydrogels were determined, and the levofloxacin drug loading capacity was calculated. The in vitro drug release studies were performed at pH 1.2 and pH 7.4 at 37°C to simulate gastric and intestinal conditions. The drug release mechanism was studied. Furthermore, the cytotoxicity results indicated that the prepared hydrogel composites have potential for biomedical applications, particularly as pH-responsive carriers for oral drug delivery.