Enhanced anticancer efficacy of docetaxel through galbanic acid encapsulated into PLA-PEG nanoparticles in treatment of colon cancer, in vitro and in vivo study

Abstract

Cancer is one of the most leading causes of human mortality and despite outstanding breakthrough in introducing new therapeutic approaches, the clinical outcomes are disappointing. Therefore, extensive research in design and preparation of more efficient drug delivery systems can open a window to shine light into the therapeutic modality. In this study, we evaluated the effect of galbanic acid (GBA) encapsulated into PLA-PEG nanoparticles (NPs) to enhanced anticancer efficacy of docetaxel (DOC) for the treatment of colon cancer. Prepared NPs were characterized by different methods in terms of size, zeta potential, and drug loading capacity. MTT assay was used to investigate the anti-proliferation of GBA-loaded PEG-PLA NPs along with DOC. The therapeutic efficacy of PEG-PLA@GBA NPs & DOC was further investigated in C26 tumor-bearing BALB/c mice model. The resulting NPs were narrowly distributed (PDI = 0.06) with the mean diameter of 148 ± 9 nm with somewhat negative charge. GBA were efficiently loaded into mPEG-PLA NPs with encapsulation efficiency of about 40% ± 3. Cytotoxicity studies showed that NPs loaded with GBA and fixed concentration of docetaxel (20 nM) have higher toxicity (IC50 = 6 ± 1.8 µM) than either PEG-PLA@GBA (IC50 = 8 ± 1.2 µM) or free GBA (IC50 = 15 ± 3.5 µM) in C26 cells. In vivo studies revealed a synergistic effect of PEG-PLA@GBA NPs and DOC on tumor growth inhibition and survival rate in comparison with monotherapy approach.