Optimized PLGA nanoparticle platform for orally dosed trans-resveratrol with enhanced bioavailability potential

Area of Science:

• Pharmacology
• Nanotechnology
• Drug Delivery

Background:

• Trans-resveratrol (t-RVT) exhibits potent antioxidant properties but suffers from extremely low oral bioavailability due to extensive first-pass metabolism and enterohepatic recirculation.
• The drug's poor bioavailability necessitates advanced formulation strategies to enable therapeutic efficacy.

Purpose of the Study:

• To develop systematically optimized (OPT) poly (dl-lactide-co-glycolide) (PLGA) nanoparticles (NPs) for trans-resveratrol (t-RVT).
• To enhance the oral bioavailability of t-RVT and overcome its inherent pharmacokinetic limitations, including enterohepatic recirculation.

Main Methods:

• Trans-resveratrol (t-RVT)-loaded PLGA NPs were fabricated using a nanoprecipitation technique.
• A 3(2) central composite design was employed to optimize NP formulation, identifying polymer and emulsifier amounts as critical factors.
• Pharmacokinetic, in vivo biodistribution, and in situ single-pass intestinal perfusion (SPIP) studies were conducted in male Wistar rats.

Main Results:

• The optimized formulation (OPT NPs) demonstrated a 7.17-fold increase in absorption rate (Ka) and a 10.6-fold increase in the area under the curve (AUC0–∞) compared to pure t-RVT and a marketed product.
• Liver concentrations of t-RVT increased 2.78-fold with the OPT formulation.
• In situ SPIP studies indicated enhanced absorptivity and permeability of OPT NPs, attributed to transport via Peyer's patches, supported by in vitro/in vivo correlation.

Conclusions:

• The developed optimized nanoparticles (OPT NPs) offer a promising strategy for significantly improving the oral bioavailability of trans-resveratrol (t-RVT).
• This nanoparticulate system effectively overcomes the challenges of enterohepatic recirculation and first-pass metabolism, providing a viable tool for enhanced t-RVT drug delivery.
• The study establishes a robust in vivo approach for evaluating nanoparticulate systems aimed at improving drug bioavailability.