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Synthesis of Cytarabine Lipid Drug Conjugate for Treatment of Meningeal Leukemia: Development, Characterization and In Vitro Cell Line Studies

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Cytarabine (Cyt) used in the treatment of meningeal leukemia is associated with drawbacks like non selectivity to tumor cells, very short half-life and inability to cross blood brain barrier (BBB) due to its hydrophilic nature. Therefore, stable lipid drug conjugate (LDC) of Cyt with stearic acid was prepared. LDC was characterized by NMR, FTIR, DSC and XRD studies. Polysorbate 80 stabilized nanoparticles of this LDC (LDC-NP) were prepared using solvent injection method and characterized for size, zeta potential and loading efficiency. The LDC-NPs were loaded with appreciable amount (considering hydrophilic nature of drug, prior to conjugation) of drug conjugate (58.39 ± 4.69%). The prepared LDC-NPs had smooth surface, particle size of 136.80 ± 3.24 nm, were non-aggregated and had almost spherical and uniform shapes. In vitro release pattern showed initial fast release (14.89 ± 0.056% in 1 h) followed by sustained release up to 72 h (76.26 ± 0.156%). The blank stearic acid nanoparticles showed no significant cytotoxic effect on leukemic EL-4 cells and LDC-NPs were more cytotoxic than Cyt solution at 48 h. The lyophilized LDC-NPs were found to be physically stable with respect to size and zeta potential at refrigerated condition for 90 days. These results suggest that Polysorbate 80 stabilized LDC-NPs can be explored for treatment of meningeal leukemia owing to their ability of providing sustained drug release, stability and improved cytotoxicity in leukemic EL-4 cell line.
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Document Type: Research Article

Publication date: 2012-12-01

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  • Journal of Biomedical Nanotechnology (JBN) is a peer-reviewed multidisciplinary journal providing broad coverage in all research areas focused on the applications of nanotechnology in medicine, drug delivery systems, infectious disease, biomedical sciences, biotechnology, and all other related fields of life sciences.
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