Development and evaluation of camptothecin loaded polymer stabilized nanoemulsion: Targeting potential in 4T1-breast tumour xenograft model

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Abstract

Targeted delivery of anticancer agents is poised to improve cancer therapy, for which polymers can serve as targeting ligands or nanocarriers for chemotherapeutic agents. In this study, we have developed and evaluated the efficacy of a camptothecin (CPT)-loaded polymer stabilized nanoemulsion (PSNE) for the passive targeted delivery to breast cancer. Based on the pseudo-ternary phase diagrams, PSNEs were developed using capmul MCM:poloxamer 407 (4:1), solutol HS 15:simulsol P23 (1:2) and water. CPT polymer mixture was developed by solvent evaporation technique. The PSNEs were characterized for droplet size distribution, plasma protein adsorption, drug release, in-vivo targeting potential, hemolytic potential, cytotoxicity, genotoxicity, in-vivo biodistribution and CPT lactone ring stability. The developed PSNEs showed uniform droplet distribution, extended drug release (76.59 ± 6.12% at 24 h), acceptable hemolytic potential, significant cytotoxicity (IC50 = 176 ± 4.3 ng/mL) and genotoxicity against MCF-7 cancer cells but low DNA damage potential in human peripheral blood lymphocytes. The efficiency of PSNEs for the targeted delivery of CPT into the tumour regions was documented in 4T1-breast tumour xenografted BALB/c mice. In-vivo biodistribution study shows that 7105.84 ± 568.46 ng/g of CPT was passively targeted from PSNE to breast cancer tissue. About 80% of the lactone form was stable for 24 h. Taken together, our study provides a promising strategy for developing PSNE-targeted drug delivery system for the breast cancer therapy.

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