Propitious maneuvering for delivery of the phytopharmaceutical “apocynin” to induced fulminant hepatitis in BALB/c mice: In vitro and in vivo assessments

Apocynin (APO), a specific nicotinamide adenine dinucleotide phosphate-oxidase (NADPH-oxidase, NOX) inhibitor, has recently emerged as a bioactive phytochemical with eminent anti-inflammatory and anti-oxidant activities. To our knowledge, no research has been conducted to fabricate a mucoadhesive nanostructured delivery system of APO that targets the liver. Accordingly, chitosan (CS) surface decorated polymeric nanoparticulate delivery system (PNDS) was victoriously fabricated by double emulsion-solvent evaporation method. Herein, a randomized full 33 factorial design was employed to assess the impact of the independently processing parameters (IPPs) namely; (poly(d,l-lactide-co-glycolide) (PLGA) amount (A)), (polyvinyl alcohol (PVA) concentration (B)), and (CS concentration (C)), on different dependently measured attributes (DMAs). The optimal APO-loaded chitosan-coated poly(d,l-lactide-co-glycolide) nanoparticles (APO-loaded CS-coated PLGA NPs) formula (F19) would be extensively appraised through meticulous in vitro-in vivo studies. Crucially, the results revealed that oral pre-treatment with the optimal formula evoked a prodigious in vivo hepatoprotective efficacy against lipopolysaccharide (LPS)/D-(+)-galactosamine (D-GalN) induced fulminant hepatitis (FH) in BALB/c mice when compared with pure APO, uncoated F19, and plain NPs (P NPs) pretreated groups. In conclusion, APO-loaded CS-coated PLGA NPs could be considered as a promising oral mucoadhesive phytopharmaceutical PNDS to open new prospects for therapeutic intervention in inflammatory based liver diseases.

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