Biodegradable self-assembled nanoparticles of PEG-PLGA amphiphilic diblock copolymer as a promising stealth system for augmented vinpocetine brain delivery.

Abstract

Vinpocetine (VNP), a semisynthetic drug, is utilized for the treatment of cerebrovascular and memory disorders. This work aimed at formulation of biodegradable VNP long-circulating nanoparticles utilizing Polyethylene glycol methyl ether-block-poly lactide-co-glycolide (PEG-PLGA) copolymer to surmount the drug drawbacks including low oral bioavailability and short elimination half-life. VNP nanoparticles were formulated using nanoprecipitation technique. A 24 factorial design was applied to assess the impact of formulation and process variables on the nanoparticles' characteristics. Statistical analysis revealed that nanoparticles size (Y1) significantly increased with increasing PEG-PLGA amount (X1), poly-vinyl alcohol concentration (X2), and PLGA content (X4), while decreased with increasing sonication time (X3). Furthermore, the entrapment efficiency (Y2) was positively affected by both PEG-PLGA amount and PLGA content, while negatively affected by poly-vinyl alcohol concentration. The optimized formulation prepared using 200mg of PEG-PLGA polymer (PEG: PLGA 2000: 4,500), 0.5% polyvinyl alcohol with sonication time of 60s achieved spherical shape with particle size of 43nm and drug entrapment of 82%. A significant bioavailability enhancement of VNP with marked prolongation of the in vivo systemic exposure of the drug and increased brain levels has also been achieved following intraperitoneal administration in Wistar rats. Thus, the optimized formulation could be regarded as a promising stealth nanocarrier that could surmount the drug pitfalls and enhance its brain delivery.