Synthesis of three-arm block copolymer poly(lactic-co-glycolic acid)–poly(ethylene glycol) with oxalyl chloride and its application in hydrophobic drug delivery

Abstract

Purpose

Synthesis of star-shaped block copolymer with oxalyl chloride and preparation of micelles to assess the prospect for drug-carrier applications.

Materials and methods

Three-arm star block copolymers of poly(lactic-co-glycolic acid) (3S-PLGA)–polyethylene glycol (PEG) were synthesized by ring-opening polymerization, then PEG as the hydrophilic block was linked to the terminal hydroxyl of 3S-PLGA with oxalyl chloride. Fourier-transform infrared (FT-IR) spectroscopy, gel-permeation chromatography (GPC), hydrogen nuclear magnetic resonance (¹H-NMR) spectra, and differential scanning calorimetry were employed to identify the structure and properties of 3S-PLGA-PEG. Rapamycin (RPM)-loaded micelles were prepared by solvent evaporation, and pyrene was used as the fluorescence probe to detect the critical micelle concentration of the copolymer. The particle size, distribution, and ζ-potential of the micelles were determined by dynamic light scattering, and the morphology of the RPM-loaded micelles was analyzed by transmission electron microscopy. High-performance liquid chromatography was conducted to analyze encapsulation efficiency and drug-loading capacity, as well as the release behavior of RPM-loaded micelles. The biocompatibility of material and the cytostatic effect of RPM-loaded micelles were investigated by Cell Counting Kit 8 assay.

Results

FT-IR, GPC, and ¹H-NMR suggested that 3S-PLGA-PEG was successfully synthesized. The RPM-loaded micelles prepared with the 3S-PLGA-PEG possessed good properties. The micelles had good average diameter and encapsulation efficiency. For in vitro release, RPM was released slowly from 3S-PLGA-PEG micelles, showing that 3S-PLGA-PEG-RPM exhibited a better and longer antiproliferative effect than free RPM.

Conclusion

In this study, we first used oxalyl chloride as the linker to synthesize 3S-PLGA-PEG successfully, and compared with reported literature, this method shortened the reaction procedure and improved the reaction yield. The micelles prepared with this material proved suitable for drug-carrier application.

Keywords:

• block copolymer
• RPM
• micelles
• cytostatic effect

Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (81271706), the Tianjin Research Foundation Advanced Technology Program (13JCZDJC30700), the Technology Foundation for Selected Overseas Chinese Scholars, Ministry of Personnel of China, and the Innovative Research Team program in Peking Union Medical College.

Disclosure

The authors report no conflicts of interest in this work.