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Investigation on design of stable etoposide-loaded PEG-PCL micelles: effect of molecular weight of PEG-PCL diblock copolymer on the in vitro and in vivo performance of micelles.

Abstract
In the present study, six different molecular weight diblock copolymer of methoxy poly (ethylene glycol)-b-poly (ε-caprolactone) (MPEG-PCL) were synthesized and characterized and was used for fabrication of etoposide-loaded micelles by nanoprecipitation technique. The particle size and percentage drug entrapment of prepared micelles were found to be dependent on the molecular weight of PCL block and drug to polymer ratio. The maximum drug loading of 5.32% was found in micellar formulation MPEG5000-PCL10000, while MPEG2000-PCL2000 exhibited 2.73% of maximum drug loading. A variation in the fixed aqueous layer thickness and PEG surface density of micellar formulations was attributed to difference in MPEG molecular weight and interaction of PEG and PCL block of copolymer. The MPEG2000-PCL2000 micelles demonstrated poor in vitro stability among other micellar formulations, due to its interaction with bovine serum albumin and immediate release of drug from micelles. Furthermore, plain etoposide and MPEG2000-PCL2000 micelles exhibited greater extent of hemolysis, due to presence of surfactants and faster release of drug from micelles, respectively. The biodistribution studies carried out on Ehrlich ascites tumor-bearing Balb/C mice confirmed higher accumulation of etoposide-loaded micellar formulation at tumor site compared to plain etoposide due to enhanced permeability and retention effect.
AuthorsMukesh Ukawala, Tushar Rajyaguru, Kiran Chaudhari, A S Manjappa, Smita Pimple, A K Babbar, Rashi Mathur, A K Mishra, R S R Murthy
JournalDrug delivery (Drug Deliv) Vol. 19 Issue 3 Pg. 155-67 (Apr 2012) ISSN: 1521-0464 [Electronic] England
PMID22364230 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Lactones
  • Micelles
  • PLC(20)-b-PEO(44)
  • Etoposide
  • Ethylene Oxide
Topics
  • Animals
  • Carcinoma, Ehrlich Tumor (drug therapy, metabolism)
  • Drug Design
  • Drug Stability
  • Ethylene Oxide (administration & dosage, chemistry, metabolism)
  • Etoposide (administration & dosage, chemistry, metabolism)
  • Female
  • Lactones (administration & dosage, chemistry, metabolism)
  • Mice
  • Mice, Inbred BALB C
  • Micelles
  • Molecular Weight
  • Treatment Outcome
  • X-Ray Diffraction

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