University of Belgrade, Faculty of Technology and Metallurgy, Department of Organic Chemical Technology, Karnegijeva 4, 11000 Belgrade, Serbia.
Int J Pharm. 2012 Oct 15;436(1-2):332-40. doi: 10.1016/j.ijpharm.2012.06.050. Epub 2012 Jun 30.
The series of poly(N-isopropylacrylamide-co-itaconic acid) hydrogels, with lipase from Candida rugosa as a model protein, were synthesized by free radical copolymerization. The composition of hydrogels was varied by monomers ratio, crosslinking agent concentration and amounts of lipase, which was loaded by in situ polymerization. All samples were characterized regarding morphology. The investigation of hydrogel swelling properties revealed their pH and temperature sensitive character. Protein loading efficiency, release profiles and the specific activity yield of the released lipase were also investigated as a function of hydrogel composition, protein content and pH, at the physiological temperature of 37 °C. Copolymers of N-isopropylacrylamide and itaconic acid presented high lipase loading efficiency. Another very important feature of these copolymers was that the protein release kinetic strongly depended on the pH value of the medium. The diffusion exponents values around 1 denoted that these hydrogel compositions could be adjusted to follow near zero-order kinetics. Namely, hydrogel formulations released low amounts of lipase at pH 2.20, but much higher released protein quantities were observed at pH 6.80 enabling these copolymers to be attractive candidates as site specific protein oral drug delivery systems.
通过自由基共聚合成了一系列聚（N-异丙基丙烯酰胺-co-衣康酸）水凝胶，以脂肪酶（Candida rugosa）作为模型蛋白。通过改变单体比例、交联剂浓度和脂肪酶用量来改变水凝胶的组成，脂肪酶通过原位聚合进行负载。所有样品均进行了形态学特征描述。水凝胶溶胀性能的研究表明其具有 pH 值和温度敏感性。还研究了蛋白负载效率、释放曲线以及在生理温度 37°C 下，水凝胶组成、蛋白含量和 pH 值对释放的脂肪酶比活的影响。N-异丙基丙烯酰胺和衣康酸的共聚物具有较高的脂肪酶负载效率。这些共聚物的另一个非常重要的特点是，蛋白质释放动力学强烈依赖于介质的 pH 值。扩散指数值接近 1 表明这些水凝胶配方可以调节以遵循近零级动力学。即在 pH 值为 2.20 时，水凝胶制剂释放的脂肪酶量较低，但在 pH 值为 6.80 时观察到释放的蛋白质量要高得多，这使得这些共聚物成为具有吸引力的口服药物的特定部位蛋白释放系统候选物。
