In vitro release of the mTOR inhibitor rapamycin from poly(ethylene glycol)-b-poly(epsilon-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, 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 alpha-tocopherol also slowed the release of rapamycin from PEG-PCL micelles in the presence of serum albumin, t50% 39 h.
Forrest
M Laird
ML
Division of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, WI 53705-2222, USA.
Won
Chee-Youb
CY
Hoffmann-La Roche, Inc., Nutley, NJ, USA.
Malick
A Waseem
AW
Hoffmann-La Roche, Inc., Nutley, NJ, USA.
Kwon
Glen S
GS
Division of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, WI 53705-2222, USA. Electronic address: gskwon@pharmacy.wisc.edu.
D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002152:Calorimetry, Differential Scanning; D005026:Ethylene Glycols; D005079:Excipients; D007700:Kinetics; D008823:Micelles; D010316:Particle Size; D011091:Polyesters; D011494:Protein Kinases / Q000187:drug effects*; D020123:Sirolimus / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D058570:TOR Serine-Threonine Kinases; D014783:Viscosity; D014961:X-Ray Diffraction; D024502:alpha-Tocopherol / Q000737:chemistry
D000900:Anti-Bacterial Agents; D005026:Ethylene Glycols; D005079:Excipients; D008823:Micelles; D011091:Polyesters; C476300:poly(epsilon-caprolactone)-b-poly(ethylene glycol); D011494:Protein Kinases; D058570:TOR Serine-Threonine Kinases; D024502:alpha-Tocopherol; D020123:Sirolimus