Institute of Fundamental Technological Research

Bone tissue possesses intrinsic regenerative capabilities to address deformities; however, its ability to repair defects caused by severe fractures, tumor resections, osteoporosis, joint arthroplasties, and surgical reconsiderations can be hindered. To address this limitation, bone tissue engineering has emerged as a promising approach for bone repair and regeneration, particularly for large-scale bone defects. In this study, an injectable hydrogel based on kappa-carrageenan-co-N-isopropyl acrylamide (κC-co-NIPAAM) was synthesized using free radical polymerization and the antisolvent evaporation technique. The κC-co-NIPAAM hydrogel's cross-linked structure was confirmed using Fourier transform infrared spectra (FTIR) and nuclear magnetic resonance (1H NMR). The hydrogel's thermal stability and morphological behavior were assessed using thermogravimetric analysis (TGA) and scanning electron microscopy (SEM), respectively. Swelling and in vitro drug release studies were conducted at varying pH and temperatures, with minimal swelling and release observed at low pH (1.2) and 25 °C, while maximum swelling and release occurred at pH 7.4 and 37oC. Cytocompatibility analysis revealed that the κC-co-NIPAAM hydrogels were biocompatible, and hematoxylin and eosin (H&E) staining demonstrated their potential for tissue regeneration and enhanced bone repair compared to other experimental groups. Notably, digital x-ray examination using an in vivo bone defect model showed that the κC-co-NIPAAM hydrogel significantly improved bone regeneration, making it a promising candidate for bone defects.

Bone regeneration, Injectable hydrogel, Nano-risedronate, Controlled delivery, Nanotechnology

The in situ injectable hydrogel system offers a widespread range of biomedical applications in prompt chronic wound treatment and management, as it provides self-healing, maintains a moist wound microenvironment, and offers good antibacterial properties. This study aimed to develop and evaluate biopolymer-based thermoreversible injectable hydrogels for effective wound-healing applications and the controlled drug delivery of meropenem. The injectable hydrogel was developed using the solvent casting method and evaluated for structural changes using proton nuclear magnetic resonance, Fourier transforms infrared spectroscopy, thermogravimetric analysis, and scanning electron microscopy. The results indicated the self-assembly of hyaluronic acid and kappa-carrageenan and the thermal stability of the fabricated injectable hydrogel with tunable gelation properties. The viscosity assessment indicated the in-situ gelling ability and injectability of the hydrogels at various temperatures. The fabricated hydrogel was loaded with meropenem, and the drug release from the hydrogel in phosphate buffer saline (PBS) with a pH of 7.4 was 96.12%, and the simulated wound fluid with a pH of 6.8 was observed to be at 94.73% at 24 h, which corresponds to the sustained delivery of meropenem. Antibacterial studies on P. aeruginosa, S. aureus, and E. coli with meropenem-laden hydrogel showed higher zones of inhibition. The in vivo studies in Sprague Dawley (SD) rats presented accelerated healing with the drug-loaded injectable hydrogel, while 90% wound closure with the unloaded injectable hydrogel, 70% in the positive control group (SC drug), and 60% in the negative control group was observed (normal saline) after fourteen days. In vivo wound closure analysis confirmed that the developed polymeric hydrogel has synergistic wound-healing potential.

bioactive polymers,thermosensitive hydrogel,biomaterials,wound repair and regeneration

Diabetic wound infection often leads to compromised healing with frequent chances of sepsis, amputation and even death. Traditional patient care emphasized on early debridement and fluid resuscitation followed by intravenous antibiotics therapy. However, compromised vasculature often limit the systemic effect of antibiotics. Current study focused formulation of chitosan HCl, κ- carrageenan and PVA based physical cross-linked hydrogel membrane dressings loaded with cefotaxime sodium (CTX), for potential diabetic burn wound healing by adopting solvent casting method. Results of mechanical strength shows tensile strength and % elongation of 12.63 0.25 and 48 respectively. Water vapor transmission rate (WVTR) depicts that despite of formulation KCP3 and KCP6, all hydrogel membranes have WVTR value in range of ideal dressing i.e., 2000–2500 g/m2/day. Whereas, all hydrogel membranes have oxygen permibility values more than 8.2 mg/ml. Bacterial penetration analysis confirms the barrier property of formulated membranes. Drug loaded hydrogel membrane showed control release up to 24 hr which provide protection against bacterial proliferation. Present study aims to constructs diabetic burn rat model which demonstrate that CTX loaded hydrogel membrane shown significantly rapid wound closure higher re-epithelization and numerous granulation tissue formation as compared to positive and negative control group. Conclusively, it is confirmed that formulated hydrogel membranes are beneficial and can be considered as a promising membrane dressing to treat diabetic burn wound.

Biomimetic membranes,Biopolymer,PVA,Diabetic wound,Wound healing Ceftriaxone

Injectable hydrogel with multifunctional tunable properties comprising biocompatibility, anti-oxidative, anti-bacterial, and/or anti-infection are highly preferred to efficiently promote diabetic wound repair and its development remains a challenge. In this study, we report hyaluronic acid and Pullulan-based injectable hydrogel loaded with curcumin that could potentiate reepithelization, increase angiogenesis, and collagen deposition at wound microenvironment to endorse healing cascade compared to other treatment groups. The physical interaction and self-assembly of hyaluronic acid-Pullulan-grafted-pluronic F127 injectable hydrogel were confirmed using nuclear magnetic resonance (1H NMR) and Fourier transformed infrared spectroscopy (FT-IR), and cytocompatibility was confirmed by fibroblast viability assay. The CUR-laden hyaluronic acid-Pullulan-g-F127 injectable hydrogel promptly undergoes a sol-gel transition and has proved to potentiate wound healing in a streptozotocin-induced diabetic rat model by promoting 93% of wound closure compared to other groups having 35%, 38%, and 62%. The comparative in vivo study and histological examination was conducted which demonstrated an expeditious recovery rate by significantly reducing the wound healing days i.e. 35 days in a control group, 33 days in the CUR suspension group, 21 days in unloaded injectable, and 13 days was observed in CUR loaded hydrogel group. Furthermore, we suggest that the injectable hydrogel laden with CUR showed a prompt wound healing potential by increasing the cell proliferation and serves as a drug delivery platform for sustained and targeted delivery of hydrophobic moieties.

Bioactive polymers,Tissue regeneration,In situ injectable hydrogel,Diabetic wound healing,Hyaluronic acid

Wounds are often recalcitrant to traditional wound dressings and a bioactive and biodegradable wound dressing using hydrogel membranes can be a promising approach for wound healing applications. The present research aimed to design hydrogel membranes based on hyaluronic acid, pullulan and polyvinyl alcohol and loaded with chitosan based cefepime nanoparticles for potential use in cutaneous wound healing. The developed membranes were evaluated using dynamic light scattering, proton nuclear magnetic resonance, Fourier transform infrared spectroscopy, thermogravimetric analysis, and scanning electron microscopy. The results indicated the novel crosslinking and thermal stability of the fabricated hydrogel membrane. The in vitro analysis demonstrates that the developed membrane has water vapors transmission rate (WVTR) between 2000 and 2500 g/m2/day and oxygen permeability between 7 and 14 mg/L, which lies in the range of an ideal dressing. The swelling capacity and surface porosity to liberate encapsulated drug (cefepime) in a sustained manner and 88% of drug release was observed. The cefepime loaded hydrogel membrane demonstrated a higher zone of inhibition against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli and excisional rat model exhibit expeditious recovery rate. The developed hydrogel membrane loaded with cefepime nanoparticles is a promising approach for topical application and has greater potential for an accelerated wound healing process.

Controlled drug delivery,Biomaterials,Hydrogel membranes,Nanoparticles,Wound healing

Objectives: The study aimed to develop safe, effective, and targeted drug delivery system for administration of nonsteroidal anti-inflammatory drugs (NSAIDs) in the form of microgels. We developed pH responsive microgels to overcome the mucosal damage caused by traditional immediate release dosage forms. Colon targeting and controlled release formulations have the potential to improve efficacy and reduce undesirable effects associated with NSAIDs.

Methods: The pH sensitive oral hydrogel demonstrates the potential to target the colon. Cellulose acetate phthalate (CAP) and hydroxyethyl methacrylate (HEMA) based microgel particles were produced using a free radical polymerization technique using ammonium persulfate (APS) initiator and methylenebisacrylamide (MBA) as the crosslinking agent. Swelling and in-vitro drug release studies were performed at a range of pH conditions. The produced formulations were characterized using Fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, scanning electron microscopy (SEM), and X-ray diffraction. Biocompatibility of the microgels was analyzed in cytotoxicity studies.

Key findings: The swelling and release rate were negligible at pH 1.2, which confirmed the pH-responsiveness of CAP-co-poly(HEMA). The co-polymeric system prevents the release of ketoprofen sodium in the stomach owing to limited swelling at gastric pH, whilst promoting release at the basic pH observed in the colon. SEM images confirmed porous nature of the microgels that facilitate effective drug diffusion through the polymeric matrix. Cytotoxicity studies revealed biocompatibility of hydrogels.

Conclusion: These investigations showed that that the controlled drug release and gastro-protective drug delivery of NSAIDS was achieved using CAP-co-poly(HEMA) microgel particles.

Biomaterials, microgels, cellulose acetate phthalate, hydrogel, pH sensitive

Ulcerative colitis (UC) is an inflammatory disease of the colon that severely affects the quality of life of patients and usually responds well to anti-inflammatory agents for symptomatic relief; however, many patients need colectomy, a surgical procedure to remove whole or part of the colon. Though various types of pharmacological agents have been employed for the management of UC, the lack of effectiveness is usually predisposed to various reasons including lack of target-specific delivery of drugs and insufficient drug accumulation at the target site. To overcome these glitches, many researchers have designed and characterized various types of versatile polymeric biomaterials to achieve target-specific delivery of drugs via oral route to optimize their targeting efficiency to the colon, to improve drug accumulation at the target site, as well as to ameliorate off-target effects of chemotherapy. Therefore, the aim of this review was to summarize and critically discuss the pharmaceutical significance and therapeutic feasibility of a wide range of natural and synthetic biomaterials for efficient drug targeting to colon and rationalized treatment of UC. Among various types of biomaterials, natural and synthetic polymer-based hydrogels have shown promising targeting potential due to their innate pH responsiveness, sustained and controlled release characteristics, and microbial degradation in the colon to release the encapsulated drug moieties. These characteristic features make natural and synthetic polymer-based hydrogels superior to conventional pharmacological strategies for the management of UC.

Ulcerative colitis, Biomaterials, Hydrogels, Biomedical applications , Ulcerative colitis

Cellulose acetate phthalate-based pH-responsive hydrogel was synthesized for fabrication of polymeric matrix tablets for gastro-protective delivery of loxoprofen sodium. Cellulose acetate phthalate (CAP) was cross-linked with methacrylic acid (MAA) using free radical polymerization technique. Fourier transform infrared (FTIR) spectra confirmed the formation of cross-linked structure of CAP-co-poly(methacrylic acid). Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) confirmed the thermal stability of polymeric networks, and scanning electron microscopy (SEM) and energy-dispersive X-ray spectrum (EDS) images unveiled that the prepared formulations were porous in nature and thus the developed formulations had shown better diffusibility. Swelling and in vitro drug release was performed at various pHs and maximum swelling and release was obtained at pH 7.4, while swelling and release rate was very low at pH 1.2 which confirmed the pH-responsive behavior of CAP-co-poly(MAA). CAP-co-poly(MAA) copolymer prevents the release of loxoprofen sodium into the stomach due to reduced swelling at gastric pH while showing significant swelling and drug release in the colon. Cytotoxicity studies revealed higher biocompatibility of fabricated hydrogel. Acute oral toxicity studies were performed for the evaluation and preliminary screening of safety profile of the developed hydrogels. Matrix tablets were evaluated for release behavior at simulated body pH. The investigations performed for analysis of hydrogels and fabricated matrix tablets indicated the controlled drug release and gastro-protective drug delivery of CAP-co-poly(MAA) hydrogels and pH-sensitive matrix tablets for targeted delivery of gastro-sensitive/irritative agents.

Acute toxicity, Cellulose acetate phthalate, Controlled release, Gastro-protective, Hydrogel

Non-healing, chronic wounds place a huge burden on healthcare systems as well as individual patients. These chronic wounds especially diabetic wounds will ultimately lead to compromised mobility, amputation of limbs and even death. Currently, wounds and limb ulcers associated with diabetes remain significant health issues; the associated healthcare cost ultimately leads to the increased clinical burden. The presence of diabetes interrupts a highly coordinated cascade of events in the wound closure process. Advances in the understanding of pathophysiological conditions associated with diabetic wounds lead to the development of drug delivery systems which can enhance wound healing by targeting various phases of the impaired processes. Wound environments typically contain degradative enzymes, along with an elevated pH and demonstrate a physiological cascade involved in the regeneration of tissue, which requires the application of an effective delivery system. This article aims to review the pathophysiological conditions associated with chronic and diabetic wounds. The delivery systems, involved in their treatment are described, highlighting potential biomaterials and polymers for establishing drug delivery systems, specifically for the treatment of diabetic wounds and the promotion of the associated mechanisms involved in advanced wound healing. Emerging approaches and engineered devices for effective wound care are reported. The discussion will give insight into the mechanisms relevant to all stages of wound healing.

Biomaterials, Diabetes, Diabetic wound healing, Hydrogels, Polymers

Oral drug delivery is natural, most acceptable and desirable route for nearly all drugs, but many drugs like NSAIDs when delivered by this route cause gastrointestinal irritation, gastric bleeding, ulcers, and many undesirable effects which limits their usage by oral delivery. Moreover, it is almost impossible to control the release of a drug in a targeted location in body. We developed thermo-responsive chitosan-co-poly(N-isopropyl-acrylamide) injectable hydrogel as an alternative for the gastro-protective and controlled delivery of loxoprofen sodium as a model drug. A free radical polymerization technique was used to synthesize thermo-responsive hydrogel by cross-linking chitosan HCl with NIPAAM using glutaraldehyde as cross-linker. Confirmation of crosslinked hydrogel structure was done by Fourier transform infrared spectra (FTIR). The thermal stability of hydrogel was confirmed through thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The scanning electron microscopy (SEM) was performed to evaluate the structural morphology of cross-linked hydrogel. To evaluate the rheological behavior of hydrogel with increasing temperature, rheological study was performed. Swelling and in vitro drug release studies were carried out under various temperature and pH conditions. The swelling study revealed that maximum swelling was observed at low pH (pH 1.2) and low temperature (25 °C) compared to the high range of pH and temperature and it resulted in quick release of the drug. The high range of pH (7.4) and temperature (37 °C) however caused controlled release of the drug. The in vivo evaluation of the developed hydrogel in rabbits demonstrated the controlled release behavior of fabricated system.

Thermosensitive hydrogels, Chitosan, NIPAAM, In vivo study, Biomaterials

The aim of this study was to develop and characterize a pH sensitive, biodegradable, interpenetrating polymeric network (IPNs) for colon specific delivery of sulfasalazine in ulcerative colitis. It also entailed in-vitro and in-vivo evaluations to optimize colon targeting efficiency, improve drug accumulation at the target site, and ameliorate the off-target effects of chemotherapy. Pectin was grafted with polyethylene glycol (PEG) and methacrylic acid (MAA) by free radical polymerization. Fourier transformed infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), energy dispersion X-ray (EDX) and powder X-ray diffraction (XRD) results confirmed the development of stable pectin-g-(PEG-co-MAA) hydrogels. The swelling and release studies exhibited that the hydrogels were capable of releasing drug specifically at colonic pH (pH 7.4). The toxicological potential of polymers, monomers and hydrogel was investigated using the Balb/c animal model, that confirmed the safety of the hydrogels. In vitro degradation of the hydrogel was evaluated using pectinase enzyme in various simulated fluids and the results showed that the hydrogels were susceptible to biodegradation by the natural microflora of the colon. In-vivo study was performed using Dextran sulphate sodium (DSS) rat model proved the hydrogels to be effective in the management of UC.

Semi-IPN hydrogel, Pectin, Sulfasalazine colon targeting, Ulcerative colitis, In vitro degradation studies, In vivo toxicity, colon targeting, colon targeting