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Abstract:
The biopolymers-based two-fold system could provide a sustained release platform for drug delivery to the brain resisting the mucociliary clearance, enzymatic degradation, bypassing the first-pass hepatic metabolism, and BBB thus providing superior bioavailability through intranasal administration. In this study, poloxamers PF-127/PF-68 grafted chitosan HCl-co-guar gum-based thermoresponsive hydrogel loaded with eletriptan hydrobromide laden pullulan nanoparticles was synthesized and subjected to dynamic light scattering, Fourier transform infrared spectroscopy, thermal analysis, x-ray diffraction, scanning electron microscopy, stability studies, mucoadhesive strength and time, gel strength, cloud point assessment, rheological assessment, ex-vivo permeation, cell viability assay, histology studies, and in-vivo Pharmacokinetics studies, etc. It is quite evident that CSG-EH-NPs T-Hgel has an enhanced sustained release drug profile where approximately 86 % and 84 % of drug released in phosphate buffer saline and simulated nasal fluid respectively throughout 48 h compared to EH-NPs where 99.44 % and 97.53 % of the drug was released in PBS and SNF for 8 h. In-vivo PKa parameters i.e., mean residence time (MRT) of 11.9 ± 0.83 compared to EH-NPs MRT of 10.2 ± 0.92 and area under the curve (AUCtot) of 42,540.5 ± 5314.14 comparing to AUCtot of EH-NPs 38,026 ± 6343.1 also establish the superiority of CSG-EH-NPs T-Hgel.

Keywords:
Biopolymers,Thermoresponsive hydrogel,Mucoadhesion,In-vivo pharmacokinetics,Nose-to-brain delivery

Abstract:
Injectable hydrogels 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 chondroitin sulphate (CS) and sodium alginate (SA)-based injectable hydrogel using solvent casting method loaded with curcumin that could potentiate reepithelization, increase angiogenesis, and collagen deposition at wound microenvironment to endorse healing cascade. The physical interaction and self-assembly of chondroitin sulfate grafted alginate (CS-Alg-g-PF127) 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 Masson's trichrome (MT) and hematoxylin and eosin (H&E) results revealed that blank chondroitin sulfate grafted alginate (CS-Alg-g-PF127) and CUR loaded CS-Alg-g-PF127 hydrogel had promising tissue regenerative ability, and showing enhanced wound healing compared to other treatment groups. The controlled release of CUR from injectable hydrogel was evaluated by drug release studies and pharmacokinetic profile (PK) using high-performance liquid chromatography (HPLC) that exhibited the mean residence time (MRT) and area under the curve (AUC) was increased up to 16.18 h and 203.64 ± 30.1 μg/mL*h, respectively. Cytotoxicity analysis of the injectable hydrogels using 3 T3-L1 fibroblasts cells and in vivo toxicity evaluated by subcutaneous injection for 24 h followed by histological examination, confirmed good biocompatibility of CUR loaded CS-Alg-g-PF127 hydrogel. Interestingly, the results of in vivo wound healing by injectable hydrogel showed the upregulation of fibroblasts-like cells, collagen deposition, and differentiated keratinocytes stimulating dermo-epidermal junction, which might endorse that they are potential candidates for excisional wound healing models.

Keywords:
Injectable hydrogels,Diabetic wound healing,Biobased thermoresponsive hydrogel,Controlled delivery,Biodegradable hydrogel