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Development and Evaluation of Nanostructured Lipid Carriers of Cytarabine for Treatment of Meningeal Leukemia

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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 °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.

Keywords: BLOOD-BRAIN BARRIER; CYTARABINE; IN-VITRO CYTOTOXICITY; MENINGEAL LEUKEMIA; NANOSTRUCTURED LIPID CARRIER

Document Type: Research Article

DOI: http://dx.doi.org/10.1166/jnn.2011.4235

Publication date: August 1, 2011

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  • Journal for Nanoscience and Nanotechnology (JNN) is an international and multidisciplinary peer-reviewed journal with a wide-ranging coverage, consolidating research activities in all areas of nanoscience and nanotechnology into a single and unique reference source. JNN is the first cross-disciplinary journal to publish original full research articles, rapid communications of important new scientific and technological findings, timely state-of-the-art reviews with author's photo and short biography, and current research news encompassing the fundamental and applied research in all disciplines of science, engineering and medicine.
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