科研之友
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摘要
The poor compatibility of carriermaterials with drugs is one of themain obstacles in the drug encapsulation of nano-drug delivery system (NDDS), hindering the clinical translation of NDDS. In this study, using paclitaxel (PTX) as the insoluble model drug, we conjugated N, N-diethylniacinamide (DENA), a hydrotropic agent of PTX, to the backbone of poly(L-g-glutamyl-glutamine) (PGG), a water-soluble polymer, to prepare the "hydrotropic polymer" PGG-DENA to improve its compatibility with PTX. By virtue of the hydrotropic effect of the DENA group, PTX was encapsulated by PGG-DENA to obtain the hydrotropic polymeric nanoparticles (PGG-DENA/PTX NPs). PTX-conjugated poly(L-gamma-glutamyl-glutamine) acid (PGG-PTX) NPs previously reported were used as the control in the study. The PGG-DENA/PTX NPs showed a z-average hydrodynamic diameter of about 70 nm, and good long-term stability in PBS solution at 4 degrees C. The cumulative release rate of PTX from PGG-DENA/PTX NPs reached 79.10% at 96 h, while that of PGG-PTX NPs was 22.96%. PGG-DENA/PTX NPs showed significantly increased in vitro cytotoxicity on NCI-H460 lung cancer cells compared with PGG-PTX NPs. The hemolysis study proved that the PGG-DENA/PTX NPs has good biocompatibility. These results indicated that by introducing the hydrotropic agent DENA, the hydrotropic polymer PGG-DENA becomes an effective carrier material of PTX. This study provides a solution to increase the compatibility of carrier materials with insoluble drugs, and also may provide an effective way to develop a series of personalized carrier materials suitable for different insoluble drugs.
