Synthesis Of Nicotinic-Acid-Based Smart Polymers And Their Application In Controlled Drug Delivery

Polymeric prodrugs are polymers that drugs are covalently bound to polymers. Because of low toxicity, high efficiency and controlled drug release, they become more and more important in biomedical field. In recent years, pH-responsive polymers have been extensively investigated. As a particular type of smart materials, they exhibited extensively potential applications. Clearly, developing a new type of pH-responsive polymeric prodrug is desirable from academic and industrial standpoints.In this paper, a nicotinic-acid-based monomer, methacryloyloxylethyl 3-pyridylformate (MAEPF) was synthesized and characterized. A range of well-defined PMAEPF polymers were synthesized via highly efficient and well controlled 2-cyanoprop-2-yl(4-fluoro) dithiobenzoate or CPFDB-mediated RAFT polymerization of MAEPF monomer under an environmentally friendly visible light radiation at 30 oC, using (2,4,6-trimethylbenzoyl) diphenylphosphine oxide (TPO) as a photo-initiator. Kinetic studies indicated that this RAFT polymerization was well-controlled. A relatively low concentration of chain transfer agent (CTA) led to both effects of shortening initialization period of this RAFT process and accelerating the overall polymerization rate. Moreover, a variety of well-defined PMAEPF-based block copolymers with poly[poly(ethylene glycol) monomethacrylate] (PPEGMA) blocks, poly(N, N-dimethylaminoethyl methacrylate) (PDMAEMA) blocks and poly(glycidyl methacrylate) (PGMA) blocks were synthesized via ambient temperature RAFT polymerization under this mild visible light radiation at 30 oC, using above-synthesized PMAEPF polymers as macro-CTA.The effect of molecular weights of PMAEPF and dipyridamole contents (DIP) on the glass transition temperature (Tg) of these polymers and blends were investigated. The results indicated that Tg of PMAEPF polymers were around 50 oC. On addition of DIP, the glass transition temperature of their blends was dramatically lowered to around room temperature. The molecular weight and structural unit ratio of PMAEPF to PPEGMA significantly affected the micellization of PMAEPF-b-PPEGMA copolymer in aqueous solution. The solution pH had negligible influence on the PMAEPF-b-PPEGMA copolymer micelles, due to the glass state of PMAEPF micellar cores at ambient temperature. However, blending DIP in PMAEPF micellar cores led to the dramatic decrease of Tg, thus facilitated the polymer chain diffusion between micelles, which caused narrow-size-distributed micelles. The drug release was remarkably accelerated on quarternization of pyridine groups and DIP in acidic solutions.