Production of paclitaxel-loaded PEG-b-PLA micelles using PEG for drug loading and freeze-drying

Abstract

A new approach named PEG-assist is introduced for the production of drug-loaded polymeric micelles. The method is based on the use of PEG as the non-selective solvent for PEG-b-PLA in the fabrication procedure. Both hydration temperature and PEG molecular weight are shown to have a significant effect on the encapsulation efficiency of PTX in PEG_4kDa-b-PLA_2kDa micelles. The optimal procedure for fabrication includes the use of PEG_1kDa as the solvent at 60 °C, cooling the mixture to 40 °C, hydration at 40 °C, freezing at -80 °C and freeze-drying at -35 °C, 15 Pa. No significant difference (p > 0.05) in PTX encapsulation, average particle size and polydispersity index is observed between the samples before freeze-drying and after reconstitution of the freeze-dried cake. The prepared PTX formulations are stable at room temperature for at least 8 h. Scaling the batch size to 25× leads to no significant change (p > 0.05) in PTX encapsulation, average particle size and polydispersity index. PEG-assist method is applicable to other drugs such as 17-AAG, and copolymers of varied molecular weights. The use of no organic solvent, simplicity, cost-effectiveness, and efficiency makes PEG-assist a very promising approach for large scale production of drug-loaded polymeric micelles.

Keywords: Diblock copolymer; Liquid-liquid phase separation; Paclitaxel; Polyethylene glycol-block-polylactic acid (PEG-b-PLA); Polymeric micelle; Scale up.