Polymer type and molecular weight dictate the encapsulation efficiency and release of Quercetin from polymeric micelles

Abstract

Flavonoids such as quercetin (QCT) represent a diverse class of natural compounds with unique therapeutic potential in cancer and inflammatory diseases. However, their clinical efficacy is hindered by poor aqueous solubility and stability. This study describes the in vitro evaluation of QCT-encapsulated polymeric micelles based on methoxy polyethylene glycol-b-poly(D,L-lactide) (mPEG-PLA) and methoxy polyethylene glycol-b-poly(e-caprolactone) (mPEG-PCL) copolymers as a drug delivery platform for QCT. The copolymers were synthesized in different molecular weights (MWs) of the hydrophobic blocks to investigate the effect of polymer type and MW on the micelle properties. All copolymers exhibited critical micelle concentrations (CMCs) in the micromolar range or lower and produced QCT-loaded micelles with particles sizes < 100 nm. mPEG5K-PLA3K, with the highest predicted compatibility with QCT as indicated by the Flory-Huggins interaction parameter, was able to achieve the highest loading capacity and encapsulation efficiency. Drug loading also exhibited a strong correlation with the hydrophilic-lipophilic balance (HLB) of the copolymers. In vitro release of the micelles followed a biphasic profile, with an initial burst phase followed by a controlled release phase, and showed a clear dependence on drug-copolymer compatibility and copolymer MW. This work represents the first report on the use of mPEG-PLA micelles to encapsulate QCT. It also emphasizes the importance of tuning formulation variables as they influence the properties of polymeric micelles for the design of a successful nanomedicine for QCT and similar drugs.