Chitosan stabilized camptothecin nanoemulsions: Development, evaluation and biodistribution in preclinical breast cancer animal mode

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 24 h), tolerable hemolytic potential (16.4 ± 1.4%), significant cytotoxicity (178 ± 4.3 ng/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 ± 174.66 ng/gm of camptothecin was passively targeted to breast cancer by CHI-CPT-NEs compared to the non-stabilized nanoemulsion (1677.58 ± 134.21 ng/gm). Thus, passive targeting of developed CHI-CPT-NEs may provide a promising approach for the efficient breast cancer therapy.