Institute of Fundamental Technological Research

The study aims to improve the solubility of poorly soluble drug by developing an optimized formulation of nanocrystals and extend its release profile by incorporating optimized nanocrystals in a biopolymer based injectable hydrogel. Nanocrystals of Silymarin (SM) were developed by anti-solvent precipitation technique followed by homogenization. Various stabilizers were investigated and combination of polyvinyl pyrrolidine K30 (PVP K30) and sodium lauryl sulfate (SLS) in a specific ratio was chosen as a stabilizer for nanocrystals. The optimized nanocrystals possessed mean particle size 172 ± 5.23 nm and PDI of 0.228 ± 0.02. Sodium alginate (Alg) and collagen (Col) based injectable hydrogel in combination with pluronic F127 showed good biocompatibility, mechanical strength and biodegradability. The developed formulation was characterized by scanning electron microscopy (SEM), thermogravimetric analysis (TGA), Fourier transform infra-red spectroscopy (FT-IR) and X-ray diffraction (XRD) analysis. The results of FT-IR and TGA showed structural cross-linking between polymers and promising thermal stability of formulation with increasing temperature, respectively. The nanocrystals loaded Alg-Col-F127 injectable hydrogel was degraded completely in 48 h. The results of in vitro release studies and in vivo pharmacokinetic profiling of silymarin nanocrystals laden Alg-Col-F127 injectable hydrogel exhibited controlled release behavior as compared to coarse silymarin suspension and silymarin nanocrystals. Therefore, nanosuspension integrated biopolymer-based hybrid injectable hydrogel system may be used to assist solubility and bioavailability enhancement as well as serve as platform to provide controlled drug release.

Nanocrystals, Injectable hydrogel, Hydrophobic drug, Solubility, Bioavailability

Hydrogels has gained tremendous interest as a controlled release drug delivery. However, currently it is a big challenge to attain high drug-loading as well as stable and sustained release of hydrophobic drugs. The poor aqueous solubility and low bioavailability of many drugs have driven the need for research in new formulations. This manuscript hypothesized that incorporation of nanocrystals of hydrophobic drug, such as silymarin into thermoreversible hydrogel could be a solution to these problems. Herein, we prepared nanocrystals of silymarin by antisolvent precipitation technique and characterized for morphology, particle size, polydispersity index (PDI) and zeta potential. Moreover, physical cross-linking of hydrogel formulations based on chondroitin sulphate (CS), kappa-Carrageenan (κ-Cr) and Pluronic® F127 was confirmed by Fourier transformed infrared spectroscopy (FT-IR). The hydrogel gelation time and temperature of optimized hydrogel was 14 ± 3.2 s and 34 ± 0.6 °C, respectively. The release data revealed controlled release of silymarin up to 48 h and in-vivo pharmacokinetic profiling was done in rabbits and further analyzed by high-performance liquid chromatography (HPLC). It is believed that the nanocrystals loaded thermoreversible injectable hydrogel system fabricated in this study provides high drug loading as well as controlled and stable release of hydrophobic drug for extended period.

Silymarin,Nanocrystals,Thermoreversible hydrogel,Drug delivery,Bioavailability

Hydrogel membrane dressings with multifunctional tunable properties encompassing biocompatibility, anti-bacterial, oxygen permeability, and adequate mechanical strength are highly preferred for wound healing. The present study aimed to develop biopolymer-based hydrogel membranes for the controlled release of therapeutic agent at the wound site. Toward this end we developed Cefotaxime sodium (CTX) loaded keratin (KR)-pullulan (PL) based hydrogel membrane dressings. All membranes show optimized vapor transmission rate (≥1000 g/ m2/day), oxygen permeability >8.2 mg/mL, MTT confirmed good biocompatibility and sufficient tensile strength (17.53 ± 1.9) for being used as a wound dressing. Nonetheless, KR-PL-PVA membranes show controlled CTX release due to enriched hydrophilic moieties which protect the wound from getting infected. In vivo results depict that CTX-KR-PL-PVA membrane group shows a rapid wound closure rate (p < 0.05) with appreciable angiogenesis, accelerated re-epithelization, and excessive collagen deposition at the wound site. These results endorsed that CTX-KR-PL-PVA hydrogel membranes are potential candidates for being used as dressing material in the diabetic wound.

Hydrogel membranes,Keratin,Diabetic wound,Wound healing,Ceftriaxone sodium

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

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