Pimenta A F R, Ascenso J, Fernandes J C S, Colaço R, Serro A P, Saramago B
Centro de Química Estrutural, Instituto Superior Técnico, University of Lisbon, Av. Rovisco Pais, 1049-001 Lisbon, Portugal; IDMEC, Departmento de Engenharia Mecânica, Instituto Superior Técnico, University of Lisbon, Av. Rovisco Pais, 1049-001 Lisbon, Portugal.
Centro de Química Estrutural, Instituto Superior Técnico, University of Lisbon, Av. Rovisco Pais, 1049-001 Lisbon, Portugal.
Int J Pharm. 2016 Dec 30;515(1-2):467-475. doi: 10.1016/j.ijpharm.2016.10.047. Epub 2016 Oct 24.
Optimization of drug delivery from drug loaded contact lenses assumes understanding the drug transport mechanisms through hydrogels which relies on the knowledge of drug partition and diffusion coefficients. We chose, as model systems, two materials used in contact lens, a poly-hydroxyethylmethacrylate (pHEMA) based hydrogel and a silicone based hydrogel, and three drugs with different sizes and charges: chlorhexidine, levofloxacin and diclofenac. Equilibrium partition coefficients were determined at different ionic strength and pH, using water (pH 5.6) and PBS (pH 7.4). The measured partition coefficients were related with the polymer volume fraction in the hydrogel, through the introduction of an enhancement factor following the approach developed by the group of C. J. Radke (Kotsmar et al., 2012; Liu et al., 2013). This factor may be decomposed in the product of three other factors E, E and E which account for, respectively, hard-sphere size exclusion, electrostatic interactions, and specific solute adsorption. While E and E are close to 1, E>>1 in all cases suggesting strong specific interactions between the drugs and the hydrogels. Adsorption was maximal for chlorhexidine on the silicone based hydrogel, in water, due to strong hydrogen bonding. The effective diffusion coefficients, D, were determined from the drug release profiles. Estimations of diffusion coefficients of the non-adsorbed solutes D=D×E allowed comparison with theories for solute diffusion in the absence of specific interaction with the polymeric membrane.
优化载药隐形眼镜的药物递送需要了解药物通过水凝胶的传输机制，这依赖于药物分配系数和扩散系数的知识。我们选择了两种用于隐形眼镜的材料作为模型系统，一种是基于聚甲基丙烯酸羟乙酯（pHEMA）的水凝胶和一种硅氧烷基水凝胶，以及三种具有不同大小和电荷的药物：氯己定、左氧氟沙星和双氯芬酸。在不同离子强度和pH值下，使用水（pH 5.6）和磷酸盐缓冲盐水（pH 7.4）测定平衡分配系数。通过引入一个增强因子，将测得的分配系数与水凝胶中的聚合物体积分数相关联，该增强因子遵循C. J. Radke小组开发的方法（Kotsmar等人，2012年；Liu等人，2013年）。这个因子可以分解为另外三个因子E、E和E的乘积，它们分别解释了硬球尺寸排阻、静电相互作用和特定溶质吸附。虽然E和E接近1，但在所有情况下E>>1，这表明药物与水凝胶之间存在强烈的特定相互作用。由于强氢键作用，氯己定在硅氧烷基水凝胶上在水中的吸附最大。有效扩散系数D是根据药物释放曲线确定的。对未吸附溶质扩散系数D=D×E的估计允许与在不存在与聚合物膜特定相互作用的情况下溶质扩散的理论进行比较。
