title: Synthesis of cytarabine lipid drug conjugate for treatment of meningeal leukemia: development, characterization and in vitro cell line studies.
abstract: 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.
authors.affiliation: Pharmacy Department, Centre for PG Studies and Research, TIFAC Centre of Relevance and Excellence in NDDS, The Maharaja Sayajirao University of Baroda, Fatehgunj, Vadodara 390002, Gujarat, India.
authors.forename: Pravin
authors.initials: P
authors.lastname: Sharma
authors.forename: Brahmanand
authors.initials: B
authors.lastname: Dube
authors.forename: Krutika
authors.initials: K
authors.lastname: Sawant
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D003561:Cytarabine / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D066298:In Vitro Techniques; D007938:Leukemia / Q000188:drug therapy*; D008055:Lipids / Q000737:chemistry*; D008577:Meningeal Neoplasms / Q000188:drug therapy*; D051379:Mice; D008956:Models, Chemical; D010316:Particle Size; D011136:Polysorbates / Q000008:administration & dosage; D013229:Stearic Acids / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008055:Lipids; D011136:Polysorbates; D013229:Stearic Acids; D003561:Cytarabine; C031183:stearic acid