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(ε-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, t50% 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 α-tocopherol also slowed the release of rapamycin from PEG–PCL micelles in the presence of serum albumin, t50% 39 h.