Development of pH-responsive gelatin/PVP nanogel by gamma radiation for controlled delivery of silibinin

Silibinin (SB) is a natural polyphenolic flavonoid with recognized health and therapeutic potential. SB has poor aqueous solubility, which limits its bioavailability and therapeutic effectiveness. To overcome these limitations, a pH-responsive gelatin/polyvinylpyrrolidone (Gel/PVP) nanogel was synthesized via γ-irradiation (5 kGy) for controlled SB delivery. SB/PVP solid dispersions were first prepared by solvent evaporation to enhance dissolution, then incorporated into the preformed Gel/PVP nanogel in the presence of N-hydroxysuccinimide (NHS), yielding the SB/Gel/PVP formulation. FTIR confirmed effective crosslinking between gelatin and PVP and successful SB encapsulation, while XRD revealed an amorphous state favorable for solubility. TEM micrograph of SB/Gel/PVP showed cubic nanoparticles < 50 nm, with a zero-point charge at pH 5.5. The nanogel achieved SB entrapment efficiency of 82% and a loading capacity of 3.34%. In vitro release studies demonstrated pH-responsive behavior, with SB release threefold higher than free drug after 6 h, and the highest release was observed at pH 4.5. The MTT assay confirmed that the SB/Gel/PVP nanogel significantly inhibited HepG2 cell proliferation compared with free SB (P < 0.05). Moreover, the biochemical and histopathological analyses of liver and kidney tissues in rats treated with SB or SB/Gel/PVP (25 mg/kg) indicated good biocompatibility. Collectively, these findings highlight Gel/PVP nanogels as a promising platform for sustained and targeted SB delivery in pharmaceutical applications.