Department of Chemical Engineering, University of Florida, Gainesville, FL 32611, USA.
Biomaterials. 2013 Apr;34(11):2814-21. doi: 10.1016/j.biomaterials.2012.12.027. Epub 2013 Jan 19.
Drug eluding contact lenses can be very effective vehicles for ophthalmic drug delivery, but are incapable of releasing drug for more than a few hours. We propose to optimize the interactions of the polymer matrix of the contact lens with the hydrophobic tails of ionic surfactants to adsorb the surfactant molecules on the polymer with high packing and thus create a high surface charge. Ionic drugs can then adsorb on the charged surfactant coated surfaces with high affinity to reduce the transport rates, leading to extended release. Specifically, we show control release of an anionic drug dexamethasone 21-disodium phosphate from poly-hydroxyethyl methacrylate (p-HEMA) contact lenses by utilizing cationic surfactant (cetalkonium chloride). The partition coefficient of the drug increase exponentially with surfactant loading in the gel in at least qualitative agreement with the Debye-Hückel theory. The drug adsorbs on the surfactant covered polymer, and can also diffuse along the surface with diffusivity lower than that for the free drug, leading to a reduction in the effective diffusivity, which is the weighted combination of the free and surface diffusivities. The addition of surfactant did not impact transparency of lenses, and had additional benefits of increase in wettability and significant reduction in protein absorption. With a surfactant loading of about 10%, the drug release duration was increased from about 2 h to 50 h in 1-day ACUVUE(®) contact lenses, proving the viability of using surfactant for increasing drug release durations.
药物缓释隐形眼镜可以作为眼科药物输送的有效载体,但只能在几个小时内释放药物。我们提出优化隐形眼镜聚合物基质与离子表面活性剂疏水尾的相互作用,将表面活性剂分子吸附在聚合物上,实现高堆积密度,从而产生高表面电荷。然后,离子药物可以通过高亲和力吸附在带电荷的表面活性剂涂层表面上,从而降低药物传输速率,实现药物的持续释放。具体来说,我们通过利用阳离子表面活性剂(十六烷基三甲基氯化铵)展示了从聚羟乙基甲基丙烯酸酯(p-HEMA)隐形眼镜中控制释放阴离子药物地塞米松 21-磷酸二钠盐。药物在凝胶中的分配系数随表面活性剂负载的增加呈指数增长,至少与 Debye-Hückel 理论定性一致。药物吸附在被表面活性剂覆盖的聚合物上,并且也可以在表面上扩散,扩散率低于游离药物,导致有效扩散率降低,这是自由扩散率和表面扩散率的加权组合。表面活性剂的添加并未影响镜片的透明度,而且还增加了润湿性,显著减少了蛋白质的吸收。在表面活性剂负载量约为 10%的情况下,在 1 天 ACUVUE®隐形眼镜中,药物释放持续时间从大约 2 小时延长至 50 小时,证明了使用表面活性剂来增加药物释放持续时间的可行性。