A multifunctional lipid nanoparticle for co-delivery of paclitaxel and curcumin for targeted delivery and enhanced cytotoxicity in multidrug resistant breast cancer cells
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Jong-Suep Baek1, Cheong-Weon Cho1
1College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Yuseong-gu, Daejeon 34134, South Korea
Cheong-Weon Cho, email: [email protected]
Keywords: solid lipid nanoparticle, multidrug resistance, p-glycoprotein, targeting delivery system, folate-mediated
Received: January 20, 2017 Accepted: February 08, 2017 Published: March 13, 2017
The objective of the work was to develop a multifunctional nanomedicine based on a folate-conjugated lipid nanoparticles loaded with paclitaxel and curcumin. The novel system combines therapeutic advantageous of efficient targeted delivery via folate and timed-release of curcumin and paclitaxel via 2-hydroxypropyl-ß-cyclodextrin, thereby overcoming multidrug resistance in breast cancer cells (MCF-7/ADR). The faster release of curcumin from the folate-conjugated curcumin and paclitaxel-loaded lipid nanoparticles enables sufficient p-glycoprotein inhibition, which allows increased cellular uptake and cytotoxicity of paclitaxel. In western blot assay, curcumin can efficiently inhibit the expression of p-glycoprotein, conformed the enhancement of cytotoxicity by paclitaxel. Furthermore, folate-conjugated curcumin and paclitaxel-loaded lipid nanoparticles exhibited increased uptake of paclitaxel and curcumin into MCF-7/ADR cells through the folate receptor-mediated internalization. Taken together, these results indicate that folate-conjugated curcumin and paclitaxel-loaded lipid nanoparticles enables the enhanced, folate-targeted delivery of multiple anticancer drugs by inhibiting the multi-drug resistance efficiently, which may also serve as a useful nano-system for co-delivery of other anticancer drugs.
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