In the current research work, pH-sensitive hydrogels were prepared via a free radical polymerization technique for the targeted delivery of 5-aminosalicylic acid to the colon. Various proportions of chitosan, β-Cyclodextrin, and acrylic acid were cross-linked by ethylene glycol dimethacrylate. Ammonium persulfate was employed as an initiator. The development of a new polymeric network and the successful encapsulation of the drug were confirmed by Fourier transform infrared spectroscopy. Thermogravimetric analysis indicated high thermal stability of the hydrogel compared to pure chitosan and β-Cyclodextrin. A rough and hard surface was revealed by scanning electron microscopy. Similarly, the crystallinity of the chitosan, β-Cyclodextrin, and fabricated hydrogel was evaluated using powder X-ray diffraction. The swelling and drug release studies were performed in both acidic and basic medium (pH 1.2 and 7.4, respectively) at 37 °C. High swelling and drug release was observed at pH 7.4 as compared to pH 1.2. The increased incorporation of chitosan, β-Cyclodextrin, and acrylic acid led to an increase in porosity, swelling, loading, drug release, and gel fraction of the hydrogel, whereas a decrease in sol fraction was observed. Thus, we can conclude from the results that a developed pH-sensitive network of hydrogel could be employed as a promising carrier for targeted drug delivery systems.

This study investigates pH-sensitive hydrogels based on biocompatible, biodegradable polysaccharides and natural polymers such as chondroitin sulfate and alginate in combination with synthetic monomer such as acrylic acid, as controlled drug carriers. Investigations were conducted for chondroitin sulfate/alginate-graft-poly(acrylic acid) hydrogel in various mixing ratios of chondroitin sulfate, alginate and acrylic acid in the presence of ammonium persulfate and N′,N′-Methylene bisacrylamide. Crosslinking and loading of drug were confirmed by Fourier transform infrared spectroscopy. Thermal stability of both polymers was enhanced after crosslinking as indicated by thermogravimetric analysis and differential scanning calorimeter thermogram of developed hydrogel. Similarly, surface morphology was evaluated by scanning electron microscopy, whereas crystallinity of the polymers and developed hydrogel was investigated by powder X-ray diffraction. Furthermore, swelling and drug-release studies were investigated in acidic and basic medium of pH 1.2 and 7.4 at 37 °C, respectively. Maximum swelling and drug release were detected at pH 7.4 as compared to pH 1.2. Increased incorporation of hydrogel contents led to an increase in porosity, drug loading, and gel fraction while a reduction in sol fraction was seen. The polymer volume fraction was found to be low at pH 7.4 compared to pH 1.2, indicating a prominent and greater swelling of the prepared hydrogels at pH 7.4. Likewise, a biodegradation study revealed a slow degradation rate of the developed hydrogel. Hence, we can conclude from the results that a fabricated system of hydrogel could be used as a suitable carrier for the controlled delivery of ketorolac tromethamine.

In this study, novel pH-responsive polymeric β-cyclodextrin-graft-poly(acrylic acid/itaconic acid) hydrogels were fabricated by the free radical polymerization technique. Various concentrations of β-cyclodextrin, acrylic acid, and itaconic acid were crosslinked by ethylene glycol dimethacrylate in the presence of ammonium persulfate. The crosslinked hydrogels were used for the controlled delivery of theophylline. Loading of theophylline was conducted by the absorption and diffusion method. The fabricated network of hydrogel was evaluated by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), X-ray diffractometry (XRD), and scanning electron microscopy (SEM). The crosslinking among hydrogel contents and drug loading by the fabricated hydrogel were confirmed by FTIR analysis, while TGA indicated a high thermal stability of the prepared hydrogel as compared to pure β-cyclodextrin and itaconic acid. The high thermal stability of the developed hydrogel indicated an increase in the thermal stability of β-cyclodextrin and itaconic acid after crosslinking. Similarly, a decrease in crystallinity of β-cyclodextrin and itaconic acid was observed after crosslinking, as evaluated by XRD analysis. SEM revealed an irregular and hard surface of the prepared hydrogel, which may be correlated with strong crosslinking among hydrogel contents. Crosslinked insoluble and uncrosslinked soluble fractions of hydrogel were evaluated by sol–gel analysis. An increase in gel fraction was seen with the increase in compositions of hydrogel contents, while a decrease in sol fraction was observed. Dynamic swelling and dissolution studies were performed in three various buffer solutions of pH 1.2, 4.6, and 7.4, respectively. Maximum swelling and drug release were observed at higher pH values as compared to the lower pH value due to the deprotonation and protonation of functional groups of the hydrogel contents; thus, the pH-sensitive nature of the fabricated hydrogel was demonstrated. Likewise, water penetration capability and polymer volume were evaluated by porosity and polymer volume studies. Increased incorporation of β-cyclodextrin, acrylic acid, and itaconic acid led to an increase in swelling, drug release, drug loading, and porosity of the fabricated hydrogel, whereas a decrease was detected with the increasing concentration of ethylene glycol dimethacrylate. Conclusively, the prepared hydrogel could be employed as a suitable and promising carrier for the controlled release of theophylline.

Ibuprofen is an antipyretic and analgesic drug used for the management of different inflammatory diseases, such as rheumatoid arthritis and osteoarthritis. Due to a short half-life and rapid elimination, multiple doses of ibuprofen are required in a day to maintain pharmacological action for a long duration of time. Due to multiple intakes of ibuprofen, certain severe adverse effects, such as gastric irritation, bleeding, ulcers, and abdominal pain are produced. Therefore, a system is needed which not only prolongs the release of ibuprofen but also overcomes the drug’s adverse effects. Hence, the authors have synthesized chondroitin sulfate/sodium polystyrene sulfonate–co-poly(acrylic acid) hydrogels by the free radical polymerization technique for the controlled release of ibuprofen. Sol-gel, porosity, swelling, and drug release studies were performed on the fabricated hydrogel. The pH-responsive behavior of the fabricated hydrogel was determined by both swelling and drug release studies in three different pH values, i.e., pH 1.2, 4.6, and 7.4. Maximum swelling and drug release were observed at pH 7.4, as compared to pH 4.6 and 1.2. Similarly, the structural arrangement and crosslinking of the hydrogel contents were confirmed by Fourier transform infrared spectroscopy (FTIR). Scanning electron microscopy (SEM) evaluated the hard and irregular surface with a few macrospores of the developed hydrogel, which may be correlated with the strong crosslinking of polymers with monomer content. Similarly, thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) demonstrated the high thermal stability of the formulated hydrogel, as compared to pure polymers. A decrease in the crystallinity of chondroitin sulfate and sodium polystyrene sulfonate after crosslinking was revealed by powder X-ray diffraction (PXRD). Thus, considering the results, we can demonstrate that a developed polymeric network of hydrogel could be used as a safe, stable, and efficient carrier for the controlled release of ibuprofen.

Arthritis conditions are widely treated with oral nonsteroidal anti-inflammatory drugs, yet long-term therapy is often limited by gastrointestinal toxicity and variable systemic exposure. To overcome these issues, an injectable thermosensitive chitosan/β-cyclodextrin-graft-poly(N-isopropylacrylamide) hydrogel was developed as a subcutaneous depot for sustained diclofenac sodium delivery. The hydrogel was synthesized via free-radical polymerization using glutaraldehyde as a crosslinker. FTIR and ¹H NMR confirmed network formation and drug incorporation, while DSC, TGA, and DTG analyses demonstrated enhanced thermal stability. SEM revealed a porous, interconnected structure, and EDX mapping verified uniform drug distribution. Rheological and swelling studies indicated shear-thinning behavior, good injectability at room temperature, rapid sol-gel transition at 37 °C, and reversible temperature-responsive swelling. In vitro release, with profiles best fitted by the Korsmeyer-Peppas model, indicating a non-Fickian diffusion-relaxation mechanism. Enzymatic degradation confirmed sufficient structural stability to support drug release for more than 10 days. HET-CAM and hemolysis assays demonstrated good biocompatibility. In vivo studies showed reduced peak plasma concentration, prolonged T_max, mean residence time, and half-life, with an approximately three-fold increase in relative bioavailability compared with the control, supporting depot-like sustained release. Overall, this thermosensitive hydrogel represents a promising platform for controlled and sustained subcutaneous drug delivery.

Injectable thermosensitive hydrogels have emerged as a promising class of biomaterials for the sustained delivery of drug. These smart systems undergo a sol-gel phase transition in response to physiological temperature, enabling minimally invasive injection and the formation of an in situ drug depot capable of controlled and sustained drug release. In recent years, thermosensitive hydrogels have drawn increasing attention in type 2 diabetes mellitus (T2DM) therapy, offering enhanced patient adherence, stable glycemic control, and reduced injection frequency compared with conventional formulations. Importantly, beyond glucose lowering, several hydrogel-based incretin therapies-particularly GLP-1 receptor agonists and dual GIP/GLP-1 agonists-have demonstrated clinically significant body-weight reduction and improved metabolic outcomes, addressing both hyperglycemia and obesity, two core components of T2DM pathophysiology. This review summarizes the classification, polymer composition, and drug release mechanisms of thermosensitive hydrogels. Special emphasis is placed on their use in the sustained delivery of insulin, GLP-1 receptor agonists and dual GIP/GLP-1 agonists. These hydrogel-based depots have demonstrated prolonged pharmacological efficacy, while preserving drug bioactivity, minimizing burst release, and achieving superior improvements in glycemic control and providing superior body-weight management with GLP-1 receptor agonists-loaded thermosensitive hydrogels, as compared with conventional injectable regimens. Finally, the challenges and future prospects of thermosensitive hydrogel systems are discussed, including the need for improved formulation stability, scalable manufacturing, and regulatory translation. With continued interdisciplinary advancements, injectable thermosensitive hydrogels hold strong potential as next-generation, long-acting, and patient-friendly delivery platforms for comprehensive diabetes management, encompassing both glycemic control and body-weight reduction in T2DM patients.