Lu Changhai, Zahedi Payam, Forman Adam, Allen Christine
Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.
J Pharm Sci. 2014 Jan;103(1):216-26. doi: 10.1002/jps.23777. Epub 2013 Nov 27.
In the present study, a series of sustained drug delivery multiarm poly(ethylene glycol) (PEG)/silica hydrogels were prepared and characterized. The hydrogels were formed by hydrolysis and condensation of poly(4-arm PEG silicate) using the sol-gel method. The relationships between water content in the PEG/silica hydrogel and stability as well as rheological properties were evaluated. Scanning electron microscopy analysis of the PEG/silica hydrogels revealed water content-dependent changes in microstructure. An increase in water content resulted in larger pores within the hydrogel, longer gelation time and higher viscosity. The PEG/silica hydrogels were loaded with dexamethasone (DMS) or dexamethasone sodium phosphate (DMSP), drugs that are hydrophobic and hydrophilic in nature, respectively. Evaluation of in vitro release revealed a zero-order release profile for DMS over the first 6 days, suggesting that degradation of the silica hydrogel matrix was the primary mechanism of drug release. It was also found that the drug-release profile could be tailored by varying the water content used during hydrogel preparation. In contrast, more than 90% of DMSP was released within 1 h, suggesting that DMSP release was only controlled by diffusion. Overall, results from this study indicate that PEG/silica hydrogels may be promising drug-eluting depot materials for the sustained delivery of hydrophobic, ophthalmic drugs.
在本研究中,制备并表征了一系列用于药物持续递送的多臂聚乙二醇(PEG)/二氧化硅水凝胶。这些水凝胶是通过溶胶-凝胶法使聚(四臂PEG硅酸盐)水解和缩合而形成的。评估了PEG/二氧化硅水凝胶中的含水量与稳定性以及流变学性质之间的关系。对PEG/二氧化硅水凝胶的扫描电子显微镜分析揭示了微观结构中与含水量相关的变化。含水量的增加导致水凝胶内的孔隙更大、凝胶化时间更长且粘度更高。PEG/二氧化硅水凝胶分别负载了地塞米松(DMS)或地塞米松磷酸钠(DMSP),这两种药物分别具有疏水性和亲水性。体外释放评估显示,DMS在最初6天呈现零级释放曲线,这表明二氧化硅水凝胶基质的降解是药物释放的主要机制。还发现可以通过改变水凝胶制备过程中使用的含水量来调整药物释放曲线。相比之下,超过90%的DMSP在1小时内释放,这表明DMSP的释放仅受扩散控制。总体而言,本研究结果表明,PEG/二氧化硅水凝胶可能是用于持续递送疏水性眼科药物的有前景的药物洗脱贮库材料。