Title : Dual-targeted biodegradable micelles for anticancer drug delivery
Abstract:
Polymeric micelles have been widely studied and developed as drug carrier for targeting solid tumors. They are able to incorporate drugs of poor water solubility in the hydrophobic core while the hydrophilic corona provides biocompatibility and prolonged circulation in blood after intravenous administration. The effectiveness of nano drug delivery may be increased by using active targeting ligands. Folate-targeted drug delivery systems can improve the tumor uptake by folate receptor-mediated endocytosis and avoid their non-specific attacks to normal tissues. Folic acid (FA) has been known to target FA receptors (FAR) that are overexpressed in several human carcinomas including breast, ovary, endometrium, kidney, lung, head and neck, brain, colon and myeloid cancers while only minimally distributed in normal tissues. Biotin receptors are often overexpressed on the surface of rapidly proliferating cancer cells. It has been found that cells that over-express folate receptors also show over-expression of biotin receptors. Moreover, tumors are heterogenous and tumor cells are substantially different from each other. Therefore, it was hypothesized that the tumor – targeting efficiency would be enhanced if the drug delivery system is decorated by both targeting molecules, which can target both vitamin receptors. Additionally, it is beneficial to incorporate more than one active agent into nanoparticles, because combination therapy is recognized as more efficient compared to conventional therapy based on a single therapeutic agent. The aim of the study was to obtain biodegradable poly(L-lactide)-co-poly(ethylene glycol) (PLA-PEG) micelles functionalized with folic acid and biotin. Paclitaxel or paclitaxel and curcumin were loaded into micelles. Encapsulation efficiency and in vitro drug delivery was studied. Finally, the in vitro cytotoxicity against Ovcar-3 cell line was studied.
The work is the result of the research project No. 2017/01/X/NZ7/00276 funded by the National Science Centre.
