In vitro release of the mTOR inhibitor rapamycin from poly(ethylene glycol)-b-poly(ε-caprolactone) micelles

An injectable formulation of rapamycin was prepared using amphiphilic block co-polymer micelles of poly(ethylene glycol)-b-poly(epsilon-caprolactone) (PEG-PCL). Drug-loaded PEG-PCL micelles were prepared by a co-solvent extraction technique. Resulting PEG-PCL micelles were less than 100 nm in diameter and contained rapamycin at 7% to 10% weight and > 1 mg/mL. PEG-PCL micelles released rapamycin over several days, t(50%) 31 h, with no burst release; however, physiological concentrations of serum albumin increased the release rate 3-fold. Alpha-tocopherol, vitamin E, was co-incorporated into PEG-PCL micelles and increased the efficiency of rapamycin encapsulation. The addition of alpha-tocopherol also slowed the release of rapamycin from PEG-PCL micelles in the presence of serum albumin, t(50%) 39 h. (c) 2005 Elsevier B.V. All rights reserved.