| Summary: | 碩士 === 國立臺灣大學 === 醫學工程學研究所 === 98 === A thermoresponsive and cationic nanoparticles based on poly(N-isopropylacrylamide-co-((2-dimethylamino)ethylmethacrylate)) copolymers (poly(NIPA-co-DMAEMA)) was fabricated by the free radical polymerization. The diameter and zeta potential of the prepared nanoparticles was about 140 nm, and 13.02 mV at 25℃, respectively. The lower critical solution temperature (LCST) of the synthesized nanoparticles was about 41℃ and higher than the human body temperature. These nanoparticles would undergo the volume phase transition when the temperature raising above the LCST. On account of the volume phase transition, the nanoparticle diameter collapsed from 140 nm to 100 nm and the size shrinkage could result in expulsion of encapsulated anticancer drugs. In this study, we successfully used the nanoparticles based on poly(NIPA-co-DMAEMA) copolymers as a drug carrier to encapsulate 7-ethyl-10-hydroxycamptothecin (SN-38). The drug encapsulation efficiency and drug loading content of SN-38/ poly(NIPA-co-DMAEMA) (D/P=1/10) nanoparticles were about 80% and 6.293%, respectively. However, the cytotoxcity of SN-38/poly(NIPA-co-DMAEMA) nanoparticles were investigated by human colon cancer cells (HT-29). The cytotoxicity effect of SN-38/poly(NIPA-co-DMAEMA) nanoparticles was elevated in HT-29 cells compared with Irinotecan® (CPT-11). In addition, the results of the drug release profile revealed that the release rate at 42℃ (above LCST) was higher than that at 37℃ (below LCST) during different periods, and the release of SN-38 molecules could be controlled by increasing the temperature. The antitumor efficacy was also evaluated in CT-26 mouse colon cancer xenograft model, indicating that the SN-38 loaded nanoparticles with hyperthermia exhibited a efficient suppression on tumor growth as compared with other treatments. Therefore, the nanoparticles based on poly(NIPA-co-DMAEMA) copolymers exhibited better temperature sensitivity and it would be an ideal carrier for drug delivery system.
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