A polymeric micelle system with a hydrolysable segment for drug delivery

Abstract

A potential anti-cancer drug-delivery polymeric micelle system with an in vitro degradation half-life of about 48 h that releases its drug upon application of ultrasound was synthesized. This vehicle was composed of an amphiphilic co-polymer, poly(ethylene oxide)-b-poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate-lactate n ). The degree of polymerization of the lactate side group, n, was 0, 3 or 5. The molar ratio of NIPAAm to HEMA-lactate n to PEO in polymerization was optimized to produce an in vitro polymeric micelle half-life of about 48 h at 40°C. 1,6-Diphenyl-1,3,5-hexatriene (DPH) was used as a fluorescent probe to study the hydrophobicity of the cores of the polymeric micelles. The results showed that the cores of the polymeric micelles were hydrophobic enough to sequester DPH and the anti-cancer drug doxorubicin (Dox). Dox was encapsulated into the polymeric micelles having a molar feed ratio of NIPAAm to HEMA-lactate3 to PEO equal to 20 : 5 : 1; this drug was released upon the application of low-frequency ultrasound. The Dox release was about 2% at room temperature and 4% at body temperature, and the drug returned to the polymeric micelles when insonation ceased.