Novel pH Sensitive Block Copolymer Micelles for Solvent Free Drug Loading

Abstract

Summary: Novel pH sensitive biodegradable block copolymers (MPEG‐PDLLA‐OSM) composed of mono‐methoxy poly(ethylene glycol) (MPEG), poly (D,L‐lactide) (PDLLA) and sulfamethazine oligomer (OSM) were synthesized via ring‐opening polymerization and a dicyclohexyl carboimide (DCC) coupling reaction. These copolymers had a relatively low critical micelle concentration (CMC) due to the strong hydrophobic properties of non‐ionized OSM at pH 7.0. Also, the pH sensitive block copolymers showed the micelle‐unimer transition due to the ionization‐non‐ionization of OSM in the pH range (pH 7.2–8.4) above the CMC. Due to the pH sensitive properties of the block copolymer, the hydrophobic drug paclitaxel (PTX) was incorporated into a pH sensitive block copolymer micelle by the pH induced micellization method, without using an organic solvent. The block copolymer micelle prepared by pH induced micellization showed a relatively high PTX loading efficiency, and good stability for 2 d at 37 °C. Furthermore, the PTX loaded micelle showed a sustained release of PTX with a small burst in vitro over 2 d. The present results suggest that the pH induced micellization method due to the micelle‐unimer transition of the pH sensitive block copolymer would be a novel and valuable drug incorporation tool for hydrophobic and protein drugs, since no organic solvent is involved in the formulation.