The improvement of diosmin dissolution by PLGA complexes for oral delivery: physicochemical characterization and anti-inflammatory evaluation

Abstract

Diosmin (DSN) is a potent flavonoid used for chronic venous insufficiency, but its therapeutic potential is constrained by poor aqueous solubility and low oral bioavailability (BCS Class IV). To overcome these challenges, a hybrid polymeric nanocarrier system comprising poly(lactic-co-glycolic acid) (PLGA) and (2-hydroxypropyl)-β-cyclodextrin (HPCD), surface-stabilized by chitosan, was successfully engineered via single-emulsion solvent evaporation. Systematic optimization identified a 95 : 5 (w/w) PLGA : HPCD formulation (95P5H-DSN), achieving an encapsulation efficiency of 71.47 ± 1.38% and a drug loading of 12.81 ± 0.25%. The nanoparticles exhibited a uniform spherical morphology with a hydrodynamic diameter of 223 ± 15.72 nm, a polydispersity index of 0.329, and a high positive zeta potential (+70.00 ± 7.35 mV), indicating good colloidal stability. Solid-state analyses (XRD, DSC, and FTIR) verified drug amorphization and successful entrapment within the matrix. In vitro release studies demonstrated pH-dependent behavior that fits the Higuchi diffusion model; the nanocarrier suppressed gastric release at pH 2.0 while providing a controlled and improved dissolution profile at intestinal pH 7.8 (17.73% at 24 h). Furthermore, in LPS-stimulated RAW264.7 macrophages, 95P5H-DSN partially attenuated the intrinsic cytotoxicity of raw DSN and exerted concentration-dependent anti-inflammatory efficacy via nitric oxide suppression. The anti-inflammatory IC50 was 58.95 µg mL−1. These findings establish the PLGA–HPCD nanocomplex as a promising oral drug-delivery platform for enhancing the dissolution and therapeutic efficacy of diosmin.