title: Development of thermosensitive poly(n-isopropylacrylamide-co-((2-dimethylamino) ethyl methacrylate))-based nanoparticles for controlled drug release.
abstract: Thermosensitive nanoparticles based on poly(N-isopropylacrylamide-co-((2-dimethylamino)ethylmethacrylate)) (poly(NIPA-co-DMAEMA)) copolymers were successfully fabricated by free radical polymerization. The lower critical solution temperature (LCST) of the synthesized nanoparticles was 41 °C and a temperature above which would cause the nanoparticles to undergo a volume phase transition from 140 to 100 nm, which could result in the expulsion of encapsulated drugs. Therefore, we used the poly(NIPA-co-DMAEMA) nanoparticles as a carrier for the controlled release of a hydrophobic anticancer agent, 7-ethyl-10-hydroxy-camptothecin (SN-38). The encapsulation efficiency and loading content of SN-38-loaded nanoparticles at an SN-38/poly(NIPA-co-DMAEMA) ratio of 1/10 (D/P = 1/10) were about 80% and 6.293%, respectively. Moreover, the release profile of SN-38-loaded nanoparticles revealed that the release rate at 42 °C (above LCST) was higher than that at 37 °C (below LCST), which demonstrated that the release of SN-38 could be controlled by increasing the temperature. The cytotoxicity of the SN-38-loaded poly(NIPA-co-DMAEMA) nanoparticles was investigated in human colon cancer cells (HT-29) to compare with the treatment of an anticancer drug, Irinotecan(®) (CPT-11). The antitumor efficacy evaluated in a C26 murine colon tumor model showed that the SN-38-loaded nanoparticles in combination with hyperthermia therapy efficiently suppressed tumor growth. The results indicate that these thermo-responsive nanoparticles are potential carriers for controlled drug delivery.
authors.affiliation: Isotope Application Division, Institute of Nuclear Energy Research, Longtan Taoyuan, Taiwan.
authors.forename: Cheng-Liang
authors.initials: CL
authors.lastname: Peng
authors.forename: Han-Min
authors.initials: HM
authors.lastname: Tsai
authors.forename: Shu-Jyuan
authors.initials: SJ
authors.lastname: Yang
authors.forename: Tsai-Yueh
authors.initials: TY
authors.lastname: Luo
authors.forename: Chia-Fu
authors.initials: CF
authors.lastname: Lin
authors.forename: Wuu-Jyh
authors.initials: WJ
authors.lastname: Lin
authors.forename: Ming-Jium
authors.initials: MJ
authors.lastname: Shieh
mesh_terms: D000042:Absorption / Q000187:drug effects; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D003692:Delayed-Action Preparations; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D005453:Fluorescence; D019073:HT29 Cells; D006801:Humans; D000077146:Irinotecan; D009682:Magnetic Resonance Spectroscopy; D008689:Methacrylates / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D036103:Nanotechnology / Q000379:methods*; D010316:Particle Size; D011109:Polymethacrylic Acids / Q000737:chemistry*; D055672:Static Electricity; D013696:Temperature; D013818:Thermogravimetry
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D008689:Methacrylates; D011109:Polymethacrylic Acids; C561402:poly(N-isopropylacrylamide-co-((2-dimethylamino)ethylmethacrylate)); D000077146:Irinotecan; C049840:2-(dimethylamino)ethyl methacrylate; D002166:Camptothecin