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Development and Characterization of Doxorubicin Bearing Vitamin B12 Coupled Sterically Stabilized Liposomes for Tumor Targeting

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The aim of the present study is to investigate the vitamin B12 conjugated doxorubicin loaded sterically stabilized liposomes for tumor targeting. Plain and sterically stabilized liposomes were prepared by modified ethanol injection method followed by remote loading of doxorubicin by ammonium sulphate gradient method. The sterically stabilized liposomes were coupled with vitamin B12 using post insertion technique. The average size of liposomes was found to be in range 105-128 nm and maximum entrapment efficiency was found to be 89.3-94.5 %. In vitro cell binding of SL-VB12 exhibits 6.28 folds higher binding to B16F10 melanoma cells in comparison to sterically stabilized liposomes. In vitro cytotoxicity study was conducted on B16F10 melanoma cells. SL-VB12 demonstrated strongest cytotoxicity to the tumor cells as compared to non targeted formulations i.e. PL and SL confirming that SL-VB12 was effectively taken up by tumor cells. The pharmacokinetic, tissue distribution and tumor growth inhibition studies were carried out followed by intravenous administration of liposomal formulations in C57BL/6 mice carrying B16F10 melanoma tumor. The half-life of SL-VB12 and SL was about 7.2 and 8.5 fold higher than that of free DOX, respectively. Accumulation of SL-VB12 in the tumor tissue was 18.9 and 2 times higher as compared to free DOX and SL respectively after 8 hours. SL-VB12 at the dose of 5 mg DOX/kg resulted in effective retardation of tumor growth. The liposomal formulation also prolong the survival time of mice as compared to free drug. Results indicate that vitamin B12 coupled liposomes bearing doxorubicin are significantly active against primary tumor than non targeted liposomes. In summary, our study indicated that the vitamin B12 coupled sterically stabilized liposomes (SL-VB12) could be used as a targeted carriers to facilitate the delivery of the encapsulated anticancer drugs into tumor cells by receptor mediated way.

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Keywords: B16F10 melanoma cells; Vitamin B12; active targeting; cancer therapy; doxorubicin loaded liposomes; sterically stabilized liposomes; transcobalamin receptors (TC-II); tumor growth inhibition; tumor specific ligands; tumor targeting; vitamin B12 coupled liposomes

Document Type: Research Article

Publication date: June 1, 2011

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  • Current Nanoscience publishes authoritative reviews and original research reports, written by experts in the field on all the most recent advances in nanoscience and nanotechnology. All aspects of the field are represented including nano- structures, synthesis, properties, assembly and devices. Applications of nanoscience in biotechnology, medicine, pharmaceuticals, physics, material science and electronics are also covered. The journal is essential to all involved in nanoscience and its applied areas.
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