Title:Preparation and In Vitro/Vivo Evaluation of Folate-conjugated Pluronic F87-PLGA/TPGS Mixed Nanoparticles for Targeted Drug Delivery
Volume: 18
Issue: 10
Author(s): Tianyi Wu, Yanchun Gong, Ziling Li, Yuping Li and Xiangyuan Xiong*
Affiliation:
- School of Life Science, Jiangxi Science and Technology Normal University, Nanchang, Jiangxi,China
Keywords:
Pluronic F87, TPGS, PLGA, nanoparticles, targeted drug delivery systems, paclitaxel.
Abstract:
Aim: Folate-conjugated Pluronic F87-poly(lactic-co-glycolic acid) block copolymer
(FA-F87-PLGA) was synthesized to encapsulate anticancer drug Paclitaxel (PTX) for targeted
drug delivery. To further improve the curative effect, D-α-tocopheryl poly(ethylene glycol) 1000
succinate (TPGS or Vitamin E TPGS) was added to form FA-F87-PLGA/TPGS mixed NPs.
Methods: FA-F87-PLGA was synthesized by the ring-opening polymerization, and the structure
was characterized. PTX-loaded nanoparticles were prepared with the nanoprecipitation method.
The physicochemical characteristics were studied to determine the appropriate dose ratio of the
FA-F87-PLGA to TPGS. The cytotoxicity against Ovarian Cancer Cells (OVCAR-3) was determined
by MTT assay. The Area Under the Curve (AUC) and half-life were measured in the in vivo
pharmacokinetic studies.
Results: Based on the optimization of particle size and embedding rate of PTX-loaded mixed NPs,
the appropriate dosage ratio of FA-F87-PLGA to TPGS was finally determined to be 5:3. According
to in vitro release studies, the cumulative release rate of PTX-loaded FA-F87-PLGA/TPGS
mixed NPs was 92.04%, which was higher than that of nanoparticles without TPGS. The cytotoxicity
studies showed that the IC50 value of PTX-loaded FA-F87-PLGA/TPGS decreased by 75.4 times
and 19.7 times after 72 h treatment compared with free PTX injections and PTX-loaded FA-F87-
PLGA NPs, respectively. In vivo pharmacokinetic studies indicated that FA-F87-PLGA/TPGS
mixed NPs had a longer drug metabolism time and a larger Area Under the Curve (AUC) compared
with free PTX injections.
Conclusion: FA-F87-PLGA/TPGS mixed NPs are potential candidates for targeted drug delivery
systems.
