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Chitosan stabilized camptothecin nanoemulsions: Development, evaluation and biodistribution in preclinical breast cancer animal mode.
International Journal of Biological Macromolecules 2017 November
Clinical use of camptothecin (CPT) is hindered due to its poor water and oil solubility, active lactone ring instability and non-targeted toxicity. Recently we reported formulation of camptothecin microemulsions with increased solubility for the improved treatment of breast cancer. In this research chitosan stabilized camptothecin nanoemulsions (CHI-CPT-NEs) were formulated improve the cancer targeting efficiency of CPT. The developed NEs were characterized for their droplet size distribution, stability in plasma and evaluated for in-vitro drug release, in-vivo targeting potential, in-vitro hemolytic potential, cytotoxicity, genotoxicity and in-vivo biodistribution. The CHI-CPT-NEs showed uniform droplet size distribution, extended drug release (61.65±1.57% at 24h), tolerable hemolytic potential (16.4±1.4%), significant cytotoxicity (178±4.3ng/ml) against MCF-7 cancer cells and low DNA damage to lymphocytes. In-vivo biodistribution study conducted in 4T1-breast tumor xenograft BALB/c mice showed that 2495.22±174.66ng/gm of camptothecin was passively targeted to breast cancer by CHI-CPT-NEs compared to the non-stabilized nanoemulsion (1677.58±134.21ng/gm). Thus, passive targeting of developed CHI-CPT-NEs may provide a promising approach for the efficient breast cancer therapy.
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