Novel thermosensitive hydrogels based on methoxy polyethylene glycol-co-poly(lactic acid-co-aromatic anhydride) for cefazolin delivery

Thermosensitive micelles composed of a copolymer of methoxy polyethylene glycol (mPEG), polylactic acid (PLA), and 1,6-bis (p-carboxyphenoxy) hexane (CPH), namely methoxy polyethylene glycol-co-polylactic acid-co-aromatic anhydride (mPEG-PLCPHA), were fabricated for application as a promising hydrophilic drug carrier. The copolymer can self-assemble into micelles in PBS by hydrophobic interaction. The diameters of these micelles increased as the environmental temperature increased. An increase in viscosity with sol-to-gel transition occurred as temperature increased from room temperature to body temperature. During the in vitro degradation process, hydrogels demonstrated a more stable degradation rate. Both in vitro and in vivo cytotoxicity results showed that the materials had excellent biocompatibility due to less acidic products formation. In vitro cefazolin release profiles showed a stable release for 30 days. The hydrogel encapsulated cefazolin exhibited a good antibacterial effect. Based on these results, mPEG-PLCPHA can serve as an injectable depot gel for drug delivery. From the Clinical Editor: In this study, thermosensitive hydrogel encapsulated cefazolin was found to exhibit good antibacterial effects with sustained levels for up to 30 days, enabling the development of an injectable depot gel for long-term drug delivery. (C) 2014 Elsevier Inc. All rights reserved.