Lipid-albumin nanoassemblies co-loaded with borneol and paclitaxel for intracellular drug delivery to C6 glioma cells with P-gp inhibition and its tumor targeting

Abstract

Successful chemotherapy with paclitaxel (PTX) is impeded by multidrug resistance (MDR) in tumor cells. In this study, lipid-albumin nanoassemblies co-loaded with borneol and paclitaxel (BOR/PTX LANs) were prepared to circumvent MDR in C6 glioma cells. The physiochemical properties including particle size, encapsulation efficiency and morphology were evaluated in vitro. Quantitative and qualitative investigations of cellular uptake were carried out in C6 glioma cells. The cytotoxicity of the BOR/PTX LANs was determined by MTT assay. After that, the tumor targeting was also evaluated in C6 glioma bearing mice by in vivo imaging analysis. BOR/PTX LANs have a higher entrapment efficiency (90.4 ± 1.2%), small particle size (107.5 ± 3.2 nm), narrow distribution (P.I. = 0.171 ± 0.02). The cellular uptake of PTX was significantly increased by BOR/PTX LANs compared with paclitaxel loaded lipid-albumin nanoassemblies (PTX LANs) in quantitative research. The result was further confirmed by confocal laser scanning microscopy qualitatively. The cellular uptake was energy-, time- and concentration-dependent, and clathrin- and endosome/lysosome-associated pathways were involved. The BOR/PTX LANs displayed a higher cytotoxicity agaist C6 glioma cells in comparion with PTX LANs and Taxol. Moreover, the encapsulation of BOR in LANs obviously increased the accumulation of the drug in tumor tissues, demonstrating the tumor targeted ability of BOR/PTX LANs. These results indicated that BOR/PTX LANs could overcome MDR by combination of drug delivery systems and P-gp inhibition, and shown the potential for treatment of gliomas.