Core–Shell Structure, Biodegradation, and Drug Release Behavior of Poly(lactic acid)/Poly(ethylene glycol) Block Copolymer Micelles Tuned by Macromolecular Stereostructure

Poly(ethylene glycol)-b-poly(L-lactic acid)-b-poly(D-lactic acid) (PEG-b-PLLA-b-PDLA) stereoblock copolymers were synthesized by sequential ring-opening polymerization. Their micelle formation, precise micelle structure, biodegradation, and drug release behavior were systematically investigated and compared with the PEG-b-poly(lactic acid) (PEG-b-PLA) diblock copolymers with various PLA stereostructures and PEG-b-PLLA/PEG-b-PDLA enantiomeric mixture. Stereoblock copolymers having comparable PLLA and PDLA block lengths and enantiomerically-mixed copolymers assemble into the stereocomplexed core-shell micelles, while the isotactic and atactic PEG-b-PLA copolymers formed the homocrystalline and amorphous micelles, respectively. The PLA segments in stereoblock copolymer micelles show smaller crystallinity than those in the isotactic and enantiomerically-mixed ones, attributed to the short block length and presence of covalent junction between PLLA and PDLA blocks. As indicated by the synchrotron radiation small-angle X-ray scattering results, the stereoblock copolymer micelles have larger size, micellar aggregation number, core radius, smaller core density, and looser packing of core-forming segments than the isotactic and enantiomerically-mixed copolymer micelles. These unique structural characteristics cause the stereoblock copolymer micelles to possess higher drug loading content, slower degradation, and drug release rates.