Poly(lactic acid)/poly(ethylene glycol) block copolymer based shell or core cross-linked micelles for controlled release of hydrophobic drug

Abstract

To improve the stability of micelles and decrease the burst release behaviours of hydrophobic drugs, poly(lactic acid)/poly(ethylene glycol) (PLA/PEG) block copolymer based shell or core cross-linked micelles are successfully fabricated. First, PLA–PEG diblock and PLA–PEG–PLA triblock copolymers terminated with acryloyl end groups are synthesized and characterized by ¹H NMR and Fourier Transform Infrared (FTIR). These PLA/PEG block copolymers can spontaneously form micelles, exposing hydrophilic PEG segments outside while hiding hydrophobic PLA segments inside the micelles. The methacryloyl groups, exposed on the outer of shell in the PLA–PEG methacrylate copolymer micelles, are copolymerized with N-vinylpyrrolidone and lead to the formation of shell cross-linked (SCL) micelles. On the contrary, the core cross-linked (CCL) micelles are fabricated through the photo-crosslinking reaction of acryloyl end groups inside the core of PLA–PEG–PLA diacrylate copolymer micelles using poly(ethylene glycol) diacrylate as cross-linker. TEM and DLS are used to investigate the morphology and size of SCL and CCL micelles. Results suggest that the size of these micelles depends on the length of PLA segments in the PLA/PEG diblock micelles and the cross-linking degree. Besides, the shell cross-linking increases the size of the micelles, while the core cross-linking decreases the size of the micelles. Notably, both SCL and CCL micelles retain higher stability than that of uncross-linked micelles. Based on these results, hydrophobic tetrandrine (TED), as the model drug, is used to evaluate the controlled release behaviours of SCL or CCL micelles. Results show that both SCL and CCL micelles can decrease the burst release phenomenon in the initial period. The release performance can be controlled via changing the length of PLA segments in the copolymers. It is indicated that these SCL or CCL micelles are useful for a hydrophobic drug-carrier system.