Stereocomplexation Assisted Assembly of Poly(γ-glutamic Acid)-graft-polylactide Nano-micelles and Their Efficacy as Anticancer Drug Carrier

Abstract

Background: Micelles as drug carriers are characterized by their inherent instability due to the weak physical interactions that facilitate the self-assembly of amphiphilic block copolymers. As one of the strong physical interactions, the stereocomplexation between the equal molar of enantiomeric polylactides, i.e., the poly(L-lactide) (PLLA) and poly(D-lactide) (PDLA), may be harnessed to obtain micelles with enhanced stability and drug loading capacity and consequent sustained release.

Aims/methods: In this paper, stereocomplexed micelles gama-PGA-g-PLA micelles) were fabricated from the stereocomplexation between poly(gama-glutamic acid)-graft-PLLA gama-PGA-g-PLA) and poly(gamaglutamic acid)-graft-PDLA gama-PGA-g-PLA). These stereocomplexed micelles exhibited a lower CMC than the corresponding enantiomeric micelles.

Result: Furthermore, they showed higher drug loading content and drug loading efficiency in addition to more sustained drug release profile in vitro. In vivo imaging confirmed that the DiR-encapsulated stereocomplexed gama-PGA-g-PLA micelles can deliver anti-cancer drug to tumors with enhanced tissue penetration. Overall, gama-PGA-g-PLA micelles exhibited greater anti-cancer effects as compared with the free drug and the stereocomplexation may be a promising strategy for fabrication of anti-cancer drug carriers with significantly enhanced efficacy.

Keywords: Poly(lactic acid); anti-cancer drug carrier; doxorubicin; micelle; poly(γ-glutamic acid); stereocomplexation..