Stable micelles formed through a stereocomplex of amphiphilic copolymers zwitterionic-(PLLA)2 and MPEG-(PDLA)2 for controlled drug delivery

Abstract

Y-Shaped amphiphilic copolymers (zwitterionic-(PLLA_2.5K)₂ and MPEG-(PDLA_2.5K)₂) were simply synthesized through click reaction of alkyne-(PLA_2.5K)₂ and zwittterionic-N₃ or MPEG-N₃. Gel permeation chromatography (GPC) and ¹H nuclear magnetic resonance (¹H NMR) were employed to characterize the composition and structure of these copolymers. The stereocomplexes were prepared from pairs zwitterionic-(PLLA_2.5K)₂/MPEG-(PDLA_2.5K)₂ (molar ratio = 1 : 1), and confirmed by differential scanning calorimeter (DSC). Furthermore the aggregation behaviors for these synthesized polymers and their stereocomplexes had been proved by fluorescence spectroscopy (PL), transmission electron microscopy (TEM), dynamic light scattering (DLS) and static light scattering (SLS), and zeta potential. Their critical micelle concentration (CMC) obtained by PL was 0.0213 mg mL⁻¹ for zwitterionic-(PLLA_2.5K)₂/MPEG_1.9K-(PDLA_2.5K)₂ and 0.1265 mg mL⁻¹ for zwitterionic-(PLLA_2.5K)₂/MPEG_5K-(PDLA_2.5K)₂. The stereocomplexes could self-assemble into spherical micelles with diameters of 76 nm (zwitterionic-(PLLA_2.5K)₂/MPEG_1.9K-(PDLA_2.5K)₂) and 89 nm (zwitterionic-(PLLA_2.5K)₂/MPEG_5K-(PDLA_2.5K)₂) respectively. The biocompatibility of these copolymers and their stereocomplexes was evaluated with relatively low cytotoxicity. The DOX-loaded micelles of the stereocomplexes had a higher drug loading content and encapsulation efficiency, and could release DOX in a controlled manner. Therefore, the new stereocomplex zwitterionic-(PLLA)₂/MPEG-(PDLA)₂ has great potential as a hydrophobic drug nanocarrier.