Improved bioavailability of orally administered andrographolide from pH-sensitive nanoparticles

Abstract

Andrographolide, a major bioactive phytoconstituent derived from Androgaphis paniculata that is safe and beneficial in several ailments, was formulated into pH-sensitive nanoparticle suspension with a view of improving its oral bioavailability. The andrographolide-loaded pH-sensitive nanoparticles were prepared by nanoprecipitation technique using Eudragit® EPO (cationic poly methacrylate copolymer). The 3(2) factorial design was used to optimize the amount of polymer and stabilizer (Pluronic® F-68). The optimized batch obtained using 0.45% w/v of Eudragit® EPO and 0.6% w/v of Pluronic® F-68 showed high-encapsulation efficiency of 93.8±0.67% with particle size of 255±9 nm and zeta potential of 29.3±3.4 mV. The bioavailability of andrographolide from optimized nanoparticles and pure andrographolide was assessed in male Wistar albino rats at a dose of 10 mg/kg. As compared to the pure andrographolide, almost 2.2 and 3.2-fold increase in AUC0-∞, Cmax and 121.53% increase in relative bioavailability were observed for andrographolide from pH-sensitive nanoparticles (P<0.05). Shorter Tmax by about fourfold difference were observed with 2.2-fold decrease in Cl/F. The improved dissolution rate owing to its reduced particle size, increased surface area and reduced diffusion layer thickness may have contributed to oral bioavailability. The results clearly indicate the potential of pH-sensitive nanoparticles for oral delivery of low-bioavailability phytoconstituents such as andrographolide.