Biotin decorated sunitinib loaded nanostructured lipid carriers for tumor targeted chemotherapy of lung cancer

Abstract

Sunitinib (SUN) is an effective and extensively used anticancer agent, but its application is greatly limited by its adverse and undesirable systemic toxic effects. The targeted delivery of SUN could reduce systemic toxicity while maintaining local anti-tumoral efficacy. In this research, a novel nanostructured lipid carrier (NLC) modified with biotin has been designed to overcome this limitation. SUN loaded biotin targeted NLCs (biotin-SUN-NLCs) were prepared by emulsion-solvent diffusion and evaporation method and optimized using irregular factorial design. The morphology of optimized NLCs was studied using SEM. The cytotoxicity of free SUN, SUN-NLCs, and biotin-SUN-NLCs and blank NLCs was evaluated on A549 cells by MTT assay. The optimized formulation presented spherical particle with a mean size of 125.50 nm, 85.10% EE, zeta potential of 10.23 mV, drug release efficiency of about 62.85% during 8 h and PdI < 0.3. Cytotoxicity of biotin-SUN-NLCs was significantly enhanced compared to that of free SUN and SUN-NLCs. The Flow cytometry and fluorescent microscope demonstrated that the biotin-NLCs exhibited higher cellular uptake in A549 human lung cells than non-targeted NLCs. In conclusion, it can be suggested that biotin-SUN-NLCs have advantages and potential for targeted lung cancer therapy.