Synthesis Of Functional Polymers-Based Nanoparticles And Its Drug Release Behaviors

Functional polymer medical nanoparticles play a very important role in the application and development of biological agents. The nanoparticles can effectively improve the security of biological agents, rationality, precision and achieve the desired effect. Polymer-based nanoparticles have obvious advantages of reducing the toxic effect of small molecule drugs, achieving the sustained release and target delivery of hydrophilic or hydrophobic drugs in body environment. Therefore, synthesis of functional polymer-based nanoparticles has caused a lot of attention from the researchers. Multifunctional drug release mechanism depends on the polymer materials that contain different functional groups. In this article, the research focuses on the construction and synthesis of multifunctional polymer-based nanoparticles and its drug release behaviors. A series of polymer-based nanoparticles has been synthesized using chitosan(CS), poly-N-isopropylacrylamide(PNIPAM) and other monomers. Finally, the drug loading efficiencies and release behaviors of nanoparticles under different conditions are investigated. The specific studies are as follows:(1) Several functionalized copolymer nanohydrogels(NHs) consisting of CS and the monomer acrylic acid(AA), methyl methacrylate(MMA) and N-isopropylacrylamide(NIPAM) are synthesized by grafting polymerization method. The loading efficiencies of 5-fluorouracil(5-FU) with different concentrations of NHs and release behaviors of 5-FU are investigated, and the release conditions of CS-based NHs are determined. Results show that the NHs possessed of a uniform spherical morphology with 140-190 nm in size and carry obvious positive charge. The maximum loading efficiencies of 5-FU is up to 99.5%. These NHs could provide a consecutive release of 5-FU in body fluid(pH 7.4), artificial gastric fluid(pH 1.2) and intestinal fluid(pH 6.8) environment.(2) The amphiphilic copolymer poly(N-isopropylacrylamide-co-acrylic acid)(P(NIPAM-co-AA)) are synthesized by free radical polymerization method. Then the cysteine is grafted on to P(NIPAM-co-AA) and P(NIPAM-co-AA)-g-Cys is prepared. Based on sonochemical method, the ultrasonic is used to radiate the mixture consists of the synthesized copolymer and hydroxyl silicone oil with hydrophobic drug template coumarin-6(C6), and then the oil phase is covered by crosslinked copolymer shell. Thus, the polymer-based MCs are successfully prepared. In order to obtain good polymer-based MCs, a series of ultrasonic conditions including the ultrasonication mode, ultrasonication power, ultrasonication time, concentrations of the polymer and water/oil ratios are systematically investigated. The optimal conditions are pulse ultrasonication mode, 250 W of ultrasonication power, 6 min of ultrasonication time, 1 wt.% of polymer concentrations and 5:1 of water to oil. The obtained polymer-based MCs possessed of a narrow size distribution and an average diameter of 1.0 μm. Additionally, the release behaviors of polymer-based MCs under different conditions are investigated. Results show that the prepared MCs possessed of stability and good drug loading capacity. The drug release experiments at different conditions prove that C6-loaded P(NIPAM-co-AA) MCs have pH- and thermo-responsive properties. And the C6-loaded P(NIPAM-co-AA)-g-Cys MCs have thermo- and redox-responsive properties. Both of the polymer-based MCs show excellent drug release behaviors.