The Synthesis Of Two Responsive Polymers And Their Application In Drug Release

Polymer-based drug delivery systems for biomedical applications and controllable release have attracted significant attentions in polymer chemistry, pharmaceutics, and biomaterials science. There are several types of polymer-based drug delivery systems, including polymer-protein conjugates, polymer-drug conjugates, micelles/nanoparticle s, and vesicles based on amphiphilic and doubly hydrophilic block copolymers, dendrimers, and hydrogels.This contribution describes two kind of responsive polymer-based drug delivery systems.1. Redox-responsive PEI hydrogels with disulfide cross-links for drug delivery Redox-responsive polyethylenimine hydrogels with disulfide cross-links were prepared by Michael addition of primary and secondary amine groups of branched PEI to disulfide cross-linker which was specifically cleaved by DTT. The prepared disulfide cross-linked hydrogels degraded into water-soluble polymers with pendant thiol (-SH) groups in the presence of the reducing agent DTT. Moreover, the resultant disulfide cross-linked hydrogels had macroporous network structure, good water-containing capability, and large BET surface area. These redox-responsive disulfide cross-linked hydrogels exhibited accelerated release of encapsulated drug in DTT containing PBS buffer solution. Furthermore, the drug release rate gradually decreased with increasing cross-linking density. Thus, it is easy to control the release rate of drug from the hydrogels by choosing appropriate cross-linking density and concentration of DTT. The disulfide cross-linked hydrogels could be utilized as noncytotoxic carriers for various hydrophilic drugs, as well as be removed easily after release in the presence of DTT.2. pH-responsive self-assembled nanoparticles of simulated graft copolymer for drug delivery.Simulated graft copolymer of poly(acrylic acid-co-stearyl acylate) [P(AA-co-SA)] and poly(ethylene glycol) (PEG) was synthesized, where acrylic acid, stearyl acylate and PEG was employed as the pH-sensitive, hydrophobic and hydrophilic segment, respectively. Polymeric nanoparticles prepared by the dialysis of simulated graft copolymer solution in dimethylformamide against citrate buffer solution with different pH values were characterized by transmission electron microscopy (TEM), fluorescence technique and laser light scattering (LLS). TEM image revealed the spherical shape of the self-aggregates, which was further confirmed by LLS measurements. The critical aggregation concentration increased markedly (10 to 150 mg/L) with increasing pH (4.6 to 7.0), in consistence with the de-protonation of carboxylic groups at higher pH. The hydrodynamic radius of polymeric nanoparticles decreased from 118 nm at pH 3.4 to 90 nm at pH 7.0. The controlled release of indomethacin from those nanoparticles was investigated, and the self-assembled nanoparticles exhibited improved performance in controlled drug release.