Teoli Deborah, Parisi Laura, Realdon Nicola, Guglielmi Massimo, Rosato Antonio, Morpurgo Margherita
University of Padova, Department of Pharmaceutical Sciences, Via Marzolo 5, 35131-Padova, Italy.
J Control Release. 2006 Dec 1;116(3):295-303. doi: 10.1016/j.jconrel.2006.09.010. Epub 2006 Sep 26.
The potential of wet sol-gel derived silica gels as new matrices for the entrapment and sustained release of proteins was investigated. Model proteins, BSA, ribonuclease-A and avidin, with differing molecular weights and/or isoelectric points, were entrapped in two silica polymer formulations having different silica contents (4% and 12% wt/v). The conformational stability of the proteins after entrapment and their release after immersion into physiological conditions were measured. Circular dichroism analysis showed that protein conformation is maintained after entrapment and stability is enhanced. Protein-free formulations were injected intramuscularly into BALB/c mice to monitor the in vivo fate of the matrix, and the results showed that the gel is totally reabsorbed, without any apparent surrounding inflammation process. The time required for matrix bioerosion varied between one to three weeks, depending on its SiO(2) content. Erosion was also measured in vitro and the contribution of erosion and diffusion to the release of the embedded proteins was quantified. These data indicate that wet silica polymers obtained by the sol-gel route are promising matrices for the sustained release of protein drugs.
研究了通过湿溶胶-凝胶法制备的硅胶作为蛋白质包封和缓释新基质的潜力。将具有不同分子量和/或等电点的模型蛋白牛血清白蛋白（BSA）、核糖核酸酶A和抗生物素蛋白包封在两种具有不同二氧化硅含量（4%和12%重量/体积）的二氧化硅聚合物配方中。测定了包封后蛋白质的构象稳定性以及浸入生理条件后的释放情况。圆二色性分析表明，包封后蛋白质构象得以维持且稳定性增强。将不含蛋白质的配方肌肉注射到BALB/c小鼠体内以监测基质在体内的命运，结果表明凝胶完全被重新吸收，没有任何明显的周围炎症过程。基质生物侵蚀所需的时间在一到三周之间，这取决于其二氧化硅含量。还进行了体外侵蚀测量，并对侵蚀和扩散对包埋蛋白质释放的贡献进行了量化。这些数据表明，通过溶胶-凝胶途径获得的湿二氧化硅聚合物是蛋白质药物缓释的有前景的基质。
