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Nanoparticles with Optimal Ratiometric Co-Delivery of Docetaxel with Gambogic Acid for Treatment of Multidrug-Resistant Breast Cancer

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It has been reported that gambogic acid (GA), the main active component of gamboge, could directly inhibit and reduce the expression level of P-gp by promoting protein degradation through post-translational proteasome pathway. In this study, the optimal molar ratio of GA/docetaxel (DTX) that could recover the sensitivity of MCF-7/ADR cells to DTX was firstly investigated. Then GA and DTX were loaded simultaneously in PLGA nanoparticles in terms of the optimal ratio. In vitro cell apoptosis and western-blot assays showed that co-delivery of anticancer drugs resulted in enhanced cell apoptosis through the downregulation of the expression level of P-gp. Interestingly, in vivo pharmacokinetic study demonstrated that GA and DTX are released synchronously in blood from the NPs. Finally, the most effective tumor growth inhibition in the MCF-7/ADR human breast tumor xenograft was observed in the co-delivery nanoparticle formulation group in comparison with saline control, free DTX solution and free DTX/GA solution. Taken together, our study demonstrated that DTX/GA PLGA NPs based combination therapy holds significant potential towards the treatment of multidrug-resistant breast cancer.
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Keywords: AAMBOGIC ACID; CO-DELIVERY; DOCETAXEL; MULTIDRUG-RESISTANCE; NANOPARTICLES

Document Type: Research Article

Publication date: September 1, 2016

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  • Journal of Biomedical Nanotechnology (JBN) is a peer-reviewed multidisciplinary journal providing broad coverage in all research areas focused on the applications of nanotechnology in medicine, drug delivery systems, infectious disease, biomedical sciences, biotechnology, and all other related fields of life sciences.
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