Preparation of Environmentally Sensitive Nanomaterials (PNIPAAm/chitosan) and Their Applications on Drug Delivery and Metal Ion Adsorption

• Main Authors: Chih-Hao Huang, 黃致豪
• Other Authors: Wen-Yen Chiu
• Format: Others
• Language: en_US
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/89634435696650001438

博士 === 國立臺灣大學 === 化學工程學研究所 === 102 === In this study, environmentally sensitive nanostructures prepared from poly(N-isopropylacrylamide) (PNIPAAm) and chitosan (CS) were designed as drug carriers or metal ion adsorbents. It contains three part researches: In the first part, we tried to prepare core-shell nanoparticles (NPs) with the diameter approximate 100 nm in order to reduce non-selective uptake by the reticuloendothelial system. We tried to in-situ synthesize PNIPAAm in the presence of chitosan (CS) micelles to prepare the environmentally sensitive NPs. Firstly, CS was found to develop a cationic micelle-like structure in the carboxylic acid solution when its concentration was increased to above the critical micelle concentration, as evidenced by fluorescence. When the NIPAAm was polymerized in the CS micelle solution by using potassium persulfate as initiator, the produced thermally sensitive PNIPAAm with anionic chain end(s) became hydrophobic, as long as the reaction temperature was above its phase transition temperature; and therefore it would diffuse into the hydrophobic core of the CS micelles, producing CS/PNIPAAm core-shell NPs. The particle size of CS/PNIPAAm NPs could reduce to 100 nm by synthesizing in the acetic acid solution. The CS/HAc/NIP-GA with average diameter of 90 nm and shrinking ratio (32.5 %) was used as a drug carrier. In the drug release study, doxycycline hyclate was sued as a model drug. The results illustrated that a gradual release behavior was observed in the solutions of 25 °C and pH 7. In the second part, the delivery systems that provide sustained release and local retention were designed to improve the efficacy of drug delivery. The thermally sensitive PNIPAAm-based nanofibrous scaffolds containing CS/HAc/NIP-GA NPs were fabricated via an electrospinning process. Firstly, thermally crosslinkable poly(NIPAAm-co-N-methylolacrylamide) (PNN) was synthesized by redox polymerization below the phase transition temperature of PNIPAAm. The phase transition temperature of the PNN copolymer could be altered from 34 to 40 oC by changing the ratio of N-methylolacrylamide (NMA) to NIPAAm. Subsequently, the CS/HAc/NIP-GA NPs were introduced into the PNN nanofibers (PNN/NPs) to achieve prolonged drug release. The nanoparticles were observed in the PNN nanofibers by transmission electron microscopy (TEM). All of the scaffolds examined had high tensile strengths (1.45 MPa or above) and exhibited no significant cytotoxicity toward human fetal skin fibroblasts. Finally, doxycycline hyclate was used as a model drug. The results illustrated that PNN/NPs nanofibrous scaffolds exhibited continuous drug release behavior in the solution of 37 °C and pH 2. In the third part, environmentally sensitive chitosan-based nanofibrous mats with highly effective desorption, reuse ability, and easy separation were prepared for metal-ion adsorption via electrospinning. The composite nanofibers were fabricated with different mass ratios of chitosan to a thermally curable copolymer, poly(NIPAAm-co-NMA). The NMA provided the function of thermal crosslinking of the nanofibrous mats to form water-stable nanofibers in aqueous solution. Subsequently, glutaraldehyde was used as a secondary crosslinking agent to increase the gel fraction of the nanofibrous mats. The swelling ratio and gel fraction of the composite nanofibrous mats were measured. The adsorption of Cu(II) and Ni(II) on the composite nanofibrous mats was investigated. The morphology changes of the nanofibers in different environments were studied. Comparing the nanofibrous mats and films of the same material, the fibrous mats showed significantly increased adsorption of Cu(II). The adsorption amount of Cu(II) on the chitosan/PNN (50/50) nanofibrous mats could reach 79 ± 2 mg/g-mats, and its desorption was relatively effective. The incorporation of poly(NIPAAm-co-NMA) significantly improved the desorption of Cu(II) from the nanofibrous mats. The chitosan/PNN fibrous mats maintained the capacity of Cu(II) adsorption for 4-time regeneration.