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Abstract:
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.

Keywords:
Nanocrystals, Injectable hydrogel, Hydrophobic drug, Solubility, Bioavailability

Abstract:
Oral drug delivery systems have innumerable advantages, despite their precedence, the delivery of lipophilic drugs belonging to biopharmaceutical class II and IV, which has challenges associated with their solubility and permeability, leading to the limitations of this route. To address these barriers, nanocarrier systems combined with biomaterials are considered one of the pre-eminent approaches. Therefore, in this study pH-responsive pullulan-based hydrogels were developed, which were loaded with curcumin nanocrystals, micelles and coarse curcumin. In-vitro characterization studies, including dynamic light scattering, Fourier-transform infrared spectroscopy, proton nuclear magnetic resonance, scanning electron microscopy, thermogravimetric analysis, differential scanning calorimetry, and X-ray diffraction supported the development of hydrogels. The swelling index showed that developed hydrogels have significant swelling at pH 7.4, as the optimized formulation shows a “q value” of 5.938% at higher pH and 2.382% at lower pH. Additionally, the nanocrystal-laden hydrogel showed 86.250% drug release at pH 7.4, and better release than micelles and coarse curcumin-laden hydrogel. Moreover, nanocrystals showed a 1-fold increase in the solubility of curcumin, enhanced physical stability, and 82.81% permeation as compared with formulations. Conclusively, the outcome of the studies distinctly revealed a promising approach for successfully developing Pu-g-MAA hydrogels and the inclusion of lipophilic drugs in them.

Keywords:
Nanocrystals, Micelles, Curcumin, Controlled release, pH sensitive, Hydrogels