Synthesis and Characterization of Thermo-Sensitive Nanoparticles for Drug Delivery Applications.

Synthesis and Characterization of Thermo-Sensitive Nanoparticles for Drug Delivery Applications.
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DOI:
10.1166/jbn.2008.014
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发表时间:
2008-12-01
影响因子:
2.9
通讯作者:
Nguyen K
Nguyen K
中科院分区:
工程技术3区
文献类型:
--
作者:
Rahimi M;Kilaru S;Sleiman GE;Saleh A;Rudkevich D;Nguyen K

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该研究项目的目的是开发新的温度敏感纳米颗粒,其具有高于体温的低临界溶解温度(LCST),并且可以与表面的各种分子结合。采用自由基聚合法合成了N-异丙基丙烯酰胺-丙烯酰胺-烯丙基胺共聚物(NIPA-AAm-AH)纳米粒子。NIPA分别与AAm和AH聚合以增加LCST并提供用于官能化的胺基。使用透射电子显微镜(TEM)和激光散射技术,这些纳米粒子的大小被发现是成反比的表面活性剂的浓度。此外,通过分光光度计测量的100-nm NIPA-AAm-AH纳米颗粒的LCST为约40 °C。用傅里叶变换红外光谱(FTIR)和核磁共振(NMR)测定的NIPA-AAm-AH纳米颗粒的化学组成也证实了每个单体的官能团的存在。纳米颗粒也成功地结合到牛抗兔IgG-德克萨斯红作为未来生物结合的模型。此外,纳米颗粒对人成纤维细胞没有显示出显著的细胞毒性活性。最后,使用多柔比星(DOX),以研究在不同温度下的NIPA-AAm-AH纳米粒的药物释放曲线。结果表明,与37 °C和4 °C相比,DOX在41 °C下释放更多,这是纳米颗粒的温度敏感性的证据。未来的工作将调查的药理学和靶向能力的合成纳米粒子共轭抗体的可能应用于控制和靶向药物输送。
The aim of this research project was to develop new temperature sensitive nanoparticles that have a lower critical solution temperature (LCST) that is above body temperature and can be incorporated with various molecules at the surface. The poly(N-isopropylacrylamide-co-acrylamide-co-allylamine) (NIPA-AAm-AH) nanoparticles were synthesized through a free radical polymerization method. NIPA was polymerized with AAm and AH to increase the LCST and to provide amine groups for functionalization, respectively. Using transmission electron microscopy (TEM) and laser scattering technology, the sizes of these nanoparticles were found to be inversely proportional to the surfactant concentrations. In addition, the LCST of the 100-nm NIPA-AAm-AH nanoparticles was approximately 40 °C measured by a spectrophotometer. The chemical composition of the NIPA-AAm-AH nanoparticles determined with Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) also confirmed the presence of functional groups of each monomer. The nanoparticles were also successfully conjugated to bovine anti-rabbit IgG-Texas Red as a model for future bioconjugation. Furthermore, nanoparticles did not show significant cytotoxicity activity against human fibroblast cells. Finally, doxorubicin (DOX) was used in order to investigate the drug release profiles of the NIPA-AAm-AH nanoparticles at different temperatures. The results indicated that DOX was released more at 41 °C compared to that of 37 °C and 4 °C, which is evidence for temperature sensitivity of the nanoparticles. Future work will investigate the pharmacological and targeted capabilities of the synthesized nanoparticles conjugated to antibodies for possible application in controlled and targeted drug delivery.
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