Synthesis and characterization of thermosensitive and pH-sensitive poly (N-isopropylacrylamide-acrylamide-vinylpyrrolidone) for use in controlled release of naltrexone.
Synthesis and characterization of thermosensitive and pH-sensitive poly (N-isopropylacrylamide-acrylamide-vinylpyrrolidone) for use in controlled release of naltrexone.
复制标题
DOI：
10.1002/jbm.a.32047
复制
发表时间：
2009-06
期刊：
影响因子：
--
通讯作者：
R. Salehi;N. Arsalani;S. Davaran;A. Entezami
中科院分区：
文献类型：
--
作者：
R. Salehi;N. Arsalani;S. Davaran;A. Entezami
采用自由基共聚法，通过改变单体投料比，合成了N-异丙基丙烯酰胺（NIPAAm）-丙烯酰胺（AAm）-乙烯基吡咯烷酮（VP）三元共聚物。用核磁共振和红外光谱确定了聚合物的组成比和结构。通过DSC检查玻璃化转变温度。采用紫外-可见光谱比浊法研究了聚合物溶液的温敏行为。聚合物溶液的溶胶-凝胶转变在1分钟内可逆地发生，响应于温度。通过改变单体投料比，合成的三元共聚物具有各自独特的低临界溶解温度（LCST）。除了热敏性，三元共聚物还表现出对pH变化的响应。随着盐的加入，缓冲溶液的离子强度的增加降低了聚合物的LCST。改变三元共聚物的相转变温度的能力为特定用途的定制转变提供了优异的灵活性。在不同温度下，在具有不同pH和离子强度的缓冲溶液中，对盘进行溶胀实验。我们研究了纳洛酮作为模型药物在磷酸盐缓冲液中的释放。载药效率在8.75 - 55%之间变化。凝胶组合物，pH值，和离子浓度影响载药量。最后，在36-37 ℃下的体外药物释放研究表明，在30天结束时，从三元共聚物中释放出35-70%的纳洛酮。此外，这些凝胶持续释放纳洛酮30天。
In this article N-isopropylacrylamide (NIPAAm)-acrylamide (AAm)-vinyl pyrrolidone (VP) terpolymers were prepared using free radical copolymerization method by varying feed ratios of monomers. The composition ratio and structure of polymer were determined by NMR and FTIR. The glass transition temperature was examined by DSC. The thermo-responsive behaviors of polymeric solutions were investigated by turbidimetry using UV-Visible spectroscopy. The sol-gel transition of the polymer solutions occurred reversibly within 1 min in response to the temperature. By alternating the monomer feed ratio, the synthesized terpolymers had their own distinctive lower critical solution temperature (LCST). In addition to the thermosensitivity, the terpolymers also showed a response to pH changes. The increase in ionic strength of the buffer solution with addition of salt lowered the LCST of the polymers. The ability to shift the phase transition temperature of the terpolymers provided excellent flexibility in tailoring transitions for specific uses. Swelling experiments were performed on the terpolymer disks in buffer solutions with different pH and ionic strength at varying temperature. We investigated naltrexone release as a model drug in phosphate buffer. Drug loading efficiency was varying from 8.75 to 55%. Gel composition, pH, and ionic concentration affected the drug loading. Finally in vitro drug release studies at 36-37 degrees C indicating 35-70% naltrexone release from terpolymers at the end of 30 days. In addition, these gels sustained naltrexone release for 30 days.