Folic acid functionalized long-circulating co-encapsulated docetaxel and curcumin solid lipid nanoparticles: In vitro evaluation, pharmacokinetic and biodistribution in rats

摘要

The purpose of this study was to develop folic acid functionalized long-circulating coencapsulated docetaxel (DTX) and curcumin (CRM) solid lipid nanoparticles (F-DC-SLN) to improve the pharmacokinetic and efficacy of DTX therapy. F-DC-SLN was prepared by hot melt-emulsification method and optimized by face centered-central composite design (FC-CCD). The SLN was characterized in terms of size and size distribution, drug entrapment efficiency and release profile. The cytotoxicity and cell uptake of the SLN formulations were evaluated in MCF-7 and MDA-MB-231 cell lines. The in vivo pharmacokinetic and biodistribution were studied in Wistar rats. F-DC-SLN exhibited 247.5 +/- 3.40 nm particle size with 73.88 +/- 1.08% entrapment efficiency and zeta potential of 14.53 +/- 3.6 mV. Transmission electron microscopy (TEM) revealed spherical morphology of the SLN. Fluorescence microscopy confirmed the targeting efficacy of F-DC-SLN in MCF-7 cells. F-DC-SLN exhibited a significant increase in area under the curve (594.21 +/- 64.34 versus 39.05 +/- 7.41 mu g/mL h) and mean residence time (31.14 +/- 19.94 versus 7.24 +/- 4.51 h) in comparison to Taxotere (R). In addition, decreased DTX accumulation from F-DC-SLN in the heart and kidney in comparison to Taxotere may avoid to toxicity these vital organs. In conclusion, the F-DC-SLN improved the efficacy and pharmacokinetic profile of DTX exhibiting enhanced potential in optimizing breast cancer therapy.