Tropical Health Institute, University of Navarra, Irunlarrea 1, E-31008 Pamplona, Spain.
Tropical Health Institute, University of Navarra, Irunlarrea 1, E-31008 Pamplona, Spain; Pharmacy and Pharmaceutical Technology Department, University of Navarra, Irunlarrea 1, E-31008 Pamplona, Spain.
Int J Pharm. 2014 Jan 1;459(1-2):1-9. doi: 10.1016/j.ijpharm.2013.11.030. Epub 2013 Dec 4.
Thermosensitive hydrogels are of a great interest due to their many biomedical and pharmaceutical applications. In this study, we synthesized a new series of random poly (methyl vinyl ether-co-maleic anhydride) (Gantrez(®) AN, GZ) and Pluronic(®) F127 (PF127) copolymers (GZ-PF127), that formed thermosensitive hydrogels whose gelation temperature and mechanical properties could be controlled by the molar ratio of GZ and PF127 polymers and the copolymer concentration in water. Gelation temperatures tended to decrease when the GZm/PF127 ratio increased. Thus, at a fixed GZm/PF127 value, sol-gel temperatures decreased at higher copolymer concentrations. Moreover, these hydrogels controlled the release of proteins such as bovine serum albumin (BSA) and recombinant recombinant kinetoplastid membrane protein of Leishmania (rKMP-11) more than the PF127 system. Toxicity studies carried out in J774.2 macrophages showed that cell viability was higher than 80%. Finally, histopathological analysis revealed that subcutaneous administration of low volumes of these hydrogels elicited a tolerable inflammatory response that could be useful to induce immune responses against the protein cargo in the development of vaccine adjuvants.
由于其在许多生物医学和药物应用中的重要性，温敏水凝胶受到了广泛关注。在本研究中，我们合成了一系列新的随机聚（甲基乙烯基醚-共-马来酸酐）（Gantrez® AN，GZ）和泊洛沙姆 F127（PF127）共聚物（GZ-PF127），这些共聚物形成的温敏水凝胶的胶凝温度和机械性能可以通过 GZ 和 PF127 聚合物的摩尔比以及共聚物在水中的浓度来控制。当 GZm/PF127 比值增加时，凝胶温度趋于降低。因此，在固定的 GZm/PF127 值下，随着共聚物浓度的增加，溶胶-凝胶温度降低。此外，与 PF127 系统相比，这些水凝胶能够控制蛋白质（如牛血清白蛋白（BSA）和重组利什曼原虫膜蛋白 11（rKMP-11））的释放。在 J774.2 巨噬细胞中进行的毒性研究表明，细胞活力高于 80%。最后，组织病理学分析表明，皮下给予低体积的这些水凝胶会引起可耐受的炎症反应，这可能有助于在疫苗佐剂的开发中诱导针对蛋白质载体的免疫反应。
