P(NIPAM/NVP)温敏性水凝胶的合成及药物缓释研究

Synthesis and Drug-delivering of P(NIPAM/NVP)Temperature-sensitive Hydrogel

以N-乙烯基吡咯烷酮(NVP)与N-异丙基丙烯酰胺(NIPAM)为原料,过硫酸铵(APS)与亚硫酸氢钠(SBS)为氧化还原引发系统,以N,N′-亚甲基双丙烯酰胺(BIS)为交联剂,采用自由基聚合的方法合成聚(N-异丙基丙烯酰胺/N-乙烯基吡咯烷酮)P(NIPAM/NVP)水凝胶。通过傅里叶变换红外光谱(FTIR)和扫描电子显微镜(SEM)对其表征,并进行溶胀度、温敏性和脉冲响应性测试,结果显示P(NIPAM/NVP)具有良好的温敏特性。利用P(NIPAM/NVP)为载体对化疗药物阿霉素(DOX)进行吸附,分别在模拟的肿瘤组织环境(pH 5.5)和正常组织环境(pH 7.4)中,25 ℃与39 ℃下进行体外药物释放研究。结果表明,P(NIPAM/NVP)具有较好的肿瘤环境响应释药性,证明P(NIPAM/NVP)在生物医学方面有着很重要的应用。

The P(NIPAM/NVP)hydrogel was synthesized by free radical polymerization method using N-Vinyl-2-pyrrolidone(NVP)and N-Isopropyl acrylamide(NIPAM)as raw material,ammonium persulphate(APS)and sodium hydrogen sulfite(SBS)as redox initiation system,N,N'-Methylenebis(2-propenamide)(BIS)as the cross-linking agent.The structure and morphology of the hydrogel were characterized by Fourier transform infrared spectrometer(FTIR)and scanning electron microscope(SEM).The swelling degree,temperature sensitivity and impulse response were measured by a series of experiments.Experiments showed that P-(NIPAM/NVP)hydrogel have network structures and good temperature sensitivity.The adsorption of doxorubicin(DOX)from aqueous solution onto P(NIPAM/NVP)hydrogel was investigated.The color of P(NIPAM/NVP)hydrogel changed from colorless to orange red through adsorption.Adsorption amount of chemotherapeutic drug doxorubicin(DOX)was measured by UV-visible spectrophotometer and the drug loading could reach 100 μg·mg^-1 .The drug release performance was carried out in a batch process and various experimental parameters such as different temperatures at different simulated ambient pH.Under different pH and temperature conditions,the cumulative drug release rate of P(NIPAM/NVP)hydrogel showed an increasing trend,then remained constant.In addition,the cumulative drug release rate at 25 ℃ was 2.6 to 5 times than that of 39 ℃ at the same pH.This was because P(NIPAM/NVP)hydrogel was a temperature-sensitive hydrogel.Under the same temperature conditions,the cumulative drug release rate of pH 5.0 was 1.7~3.5 times than that of pH 7.4.Under different temperature and pH conditions,the cumulative release rate of P(NIPAM/NVP)hydrogel showed an increasing trend with time,and finally reached the release equilibrium.Meanwhile,the drug accumulation and release rate of P(NIPAM/NVP)hydrogel at pH 5.0 was always greater than at pH 7.4.The results showed that the synthesized P(NAPIM/NVP)hydrogel exhibit good temperature-sensitivity.In addition,DOX loading and release tests proved that the hydrogel has potential applications in biomedical field.