Physical and Pharmacokinetic Characterizations of trans-Resveratrol (t-Rev) Encapsulated with Self-Assembling Lecithin-based Mixed Polymeric Micelles (saLMPMs)

Abstract

This study involved physical and pharmacokinetic characterizations of trans-resveratrol (t-Rev)-loaded saLMPMs which attempted to improve t-Rev's pharmacokinetic profiles and bioavailability resolving hurdles limiting its potential health benefits. The optimal formulation consisted of t-Rev, lecithin, and Pluronic® P123 at 5:2:20 (t-Rev-loaded PP123 saLMPMs) provided mean particle size <200 nm, encapsulation efficiency >90%, and drug loading >15%. Compared to t-Rev solubilized with HP-β-CD, t-Rev-loaded PP123 saLMPMs enhanced t-Rev's stability in PBS at RT, 4 °C, and 37 °C and in FBS at 37 °C, and retarded the in vitro release. Intravenous administration of t-Rev-loaded PP123 saLMPMs was able to enhance 40% absolute bioavailability and a greater portion of t-Rev was found to preferably distribute into peripheral compartment potentially establishing a therapeutic level at the targeted site. With oral administration, t-Rev-loaded LMPMs increases 2.17-fold absolute bioavailability and furnished a 3-h period of time in which the plasma concentration maintained above the desirable concentration for chemoprevention and accomplished a higher value of the dose-normalized area under the curve for potentially establishing an effective level at the target site. Therefore, intravenous and oral pharmacokinetic characteristics of t-Rev encapsulated with PP123 saLMPMs indicate that t-Rev can be translated into a clinically useful therapeutic agent.