Study On Hydrotropic Effect-based Paclitaxel-loaded Self-assembled Polymeric Nanoparticles

The poor compatibility of drugs and carrier materials is the leading cause of low drug-loading capacity and poor stability of nano-drug delivery system(NDDS),and these two problems have become the main obstacles in the process of the clinical application of NDDS.In view of above problems,this project aims to conjugating hydrotropic agents of poorly soluble drugs to the molecular structure of polymeric materials,in order to increase the compatibility of carrier materials and drugs,thereby improving the drug-loading capacity and stability of NDDS.Specifically,using paclitaxel(PTX)as the model drug,we will conjugate N,N-diethyl niacinamide(DENA),the hydrotropic agents of PTX,to the backbone of Poly(L-?-glutamylglutamine)(PGG),a water-soluble polymer,to prepare the "hydrotropic polymer" PGG-DENA.Then by virtue of the hydrotropic effect of DENA group,PTX can be encapsulated by PGG-DENA to obtain the hydrotropic polymeric nanoparticles PGG-DENA/PTX with high drug-loading capacity and stability.Finally,the structure of PGG-DENA can be optimized based on the evaluation of physical and chemical properties and in vivo and in vitro biological effects of PGG-DENA/PTX.The idea of this project can also be applied to other poorly soluble drugs,and guide the design and synthesis of a series of personalized hydrotropic polymers suitable for different drugs,thereby improving the druggability,and providing an effective way for promoting the process of clinical application of NDDS in our country.