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Development and evaluation of nanostructured lipid carriers of cytarabine for treatment of meningeal leukemia.

Abstract
Lipid matrix based carriers are able to provide sustained release, increase the drug transport into cancer cells and overcome the drug resistance. Therefore, nanostructured lipid carriers (NLC) were prepared and coated with polysorbate 80 to overcome the blood brain barrier for achieving effective treatment of meningeal leukemia. NLC were prepared by melt emulsification followed by ultrasonication, producing particles of 90.7 +/- 4.28 nm size with appreciable amount of drug entrapment (49.5 +/- 2.24%), considering the hydrophilic nature of the drug. The polysorbate 80 coated cytarabine loaded NLC (Cyt-NLC) thus produced were non-aggregated and had almost spherical, smooth and uniform shape. Results of DSC and XRD studies indicated that Cyt was entrapped inside the lipid as molecular dispersion. In-vitro release pattern showed initial fast release (15.87 +/- 1.524% in 1 h) followed by sustained release upto 72 h (89.90 +/- 1.11%). In-vitro cell line studies demonstrated that blank NLC showed no significant cytotoxic effects on leukemic EL-4 cells whereas Cyt-NLC exhibited concentration dependent cytotoxicity. At 48 and 72 h, cytotoxicity of Cyt-NLC was found to be significantly more than that of Cyt solution and the percentage cell viability decreased with increasing concentration of Cyt-NLC. The lyophilized Cyt-NLC formulation was found to be stable with respect to size and total drug content at refrigerated condition (2-8 degrees C) for 3 months. These results suggest that polysorbate 80 coated Cyt-NLC can be explored for treatment of meningeal leukemia owing to their ability of sustained drug release and improved cytotoxic effect in leukemic EL-4 cell line.
AuthorsPraveen Sharma, Brahmanand Dube, Krutika Sawant
JournalJournal of nanoscience and nanotechnology (J Nanosci Nanotechnol) Vol. 11 Issue 8 Pg. 6676-82 (Aug 2011) ISSN: 1533-4880 [Print] United States
PMID22103067 (Publication Type: Journal Article)
Chemical References
  • Drug Carriers
  • Lipids
  • Cytarabine
Topics
  • Calorimetry, Differential Scanning
  • Cytarabine (administration & dosage)
  • Drug Carriers
  • Humans
  • Leukemia (drug therapy)
  • Lipids (administration & dosage)
  • Meningeal Neoplasms (drug therapy)
  • Microscopy, Electron, Transmission
  • Nanostructures
  • Particle Size
  • Powder Diffraction

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