Preparation Of Polyion Complex Micelles And The Application In Drug Controlled Release Systems

Drug-controlled release systems have great benefits for patients such as therapeutic effect, reduced toxicity, lessened drug-taken times, and so on. It is greatly meaningful for improving the level of clinic therapy. Thereby, it has been attracting more and more attentions. Over the last two decades, this field has witnessed the emergence of nanoscale systems such as polymeric micelles, nanoparitcles, polymer conjugates and hydrogels. In particular, polymeric micelles are currently recognized as one of the most promising modalities of drug carriers because of their several advantages including high drug efficiency, targeted delivery and minimized cytotoxicity. Polymeric micelles have a unique core-shell structure and the hydrophobic core may act as a microreservoir for various pharmaceutical agents. Furthermore, entrapment of the drug in the core was shown to protect it from in vivo metabolism or enzymatic degradation. According to the type of intermolecular forces driving the segregation of the core segment in the aqueous milieu, polymeric micelles can be classed as amphiphilic micelles, polyion complex (PIC) micelles, and micelles stemming from metal complexation. Amphiphilic micelles are formed by amphiphilic block copolymers in which the hydrophilic blocks form the outer shell of the micelle and the hydrophobic blocks form the inner core. From the drug delivery point of view, amphiphilic micelles have unique characteristics such as nanosize, good biocompatibility, thermodynamic stability in physiological conditions and a preventive against interaction with proteins and cells. However, there is a drawback that they cannot incorporate ionic species into the core because the core is hydrophobic in nature. PIC micelles, formed by electrostatic interaction between a pair of oppositely charged block copolymers, combine features of amphiphilic micelles and interpolyelectrolyte complexes. Due to the hydrophobic and ionic nature of the core, the PIC micelles can not only incorporate the water insoluble drug through hydrophobic interaction, but also incorporate ionic drug through electrostatic interactions. Moreover, this system has been successfully used for the delivery of charged drugs such as oligonucleotides, DNA, and enzymes.In this paper, double hydrophilic block copolymers, poly(N-vinylprrolidone)- block-poly(styrene-alter-maleic anhydride) (PVP-b-PSMA), poly(N-vinylprroli-done)-block-poly(N, N-dimethylaminoethyl methacrylate) (PVP-b-PDMAEMA) and poly(N-vinylprroli- done)-block-poly(2-acrylamido-2-methyl-1 -propanesulfonic acid) (PVP-b-PAMPS) were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. In aqueous media, a pair of oppositely-charged diblock copolymers could self-assemble into stable and narrow distribution PIC micelles. Transmission electron micrographs (TEM) and dynamic light scattering (DLS) analysis showed that the micelles to be spherically shaped with mean hydrodynamic diameter. In addition, the PIC micelles display ability to response to external stimuli. All of theses features are quite feasible for utilizing it as a novel intelligent drug delivery system. In order to assess its application in biomedical area, release profiles of coenzyme A (Co A)from PIC micelles were studied under different conditions. The results of experiment indicate that the PIC micelles have marked drug release behavior on the water-soluble drug.