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

• Published in: Journal of controlled release 2006-01, Vol.110 (2), p.370-377
• Main Authors: Forrest, M. Laird, Won, Chee-Youb, Malick, A. Waseem, Kwon, Glen S.
• Format: Article
• Language: English
• Subjects: Algorithms; alpha-Tocopherol - chemistry; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - pharmacokinetics; Biological and medical sciences; Calorimetry, Differential Scanning; Ethylene Glycols; Excipients; General pharmacology; Kinetics; Medical sciences; Micelles; mTOR; Nanocarrier; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Poly(ethylene glycol)-b-poly(ε-caprolactone); Polyesters; Polymer micelle; Protein Kinases - drug effects; Rapamycin; Sirolimus - administration & dosage; Sirolimus - pharmacokinetics; TOR Serine-Threonine Kinases; Viscosity; X-Ray Diffraction
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2005.10.008

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.