a Biomimetic & Biohybrid Materials, Biomedical Devices, & Drug Delivery Laboratories, Department of Chemical Engineering , Auburn University , Auburn , AL , 36849 , USA .
J Biomater Sci Polym Ed. 2014;25(1):88-100. doi: 10.1080/09205063.2013.840228. Epub 2013 Sep 27.
To alter the composition and structure of silicone hydrogel contact lenses to achieve controlled release of dexamethasone and evaluate the lens optical and mechanical properties compared to commercial lenses. There is a tremendous need for controlled release of drugs from ocular biomaterials as the majority of ophthalmic drugs are delivered via topical eye drops, which have low bioavailability and patient compliance.
Poly(PDMS-co-TRIS-co-DMA) contact lenses were synthesized with varying PDMS/TRIS:DMA ratios (0.25:1, 0.67:1, 1.5:1) as well as with additional crosslinking monomers. Lenses were characterized via in vitro release studies in a microfluidic device at ocular flowrates and in large well-mixed volumes, optical quality studies over visible wavelengths, mechanical analysis, and determination of polymer volume fraction in the swollen state.
Extended and controlled release of therapeutically relevant concentrations of dexamethasone was achieved for multiple day, continuous wear up to 60 days at in vitro ocular flowrates. Release was delayed due to a combination of increased hydrophobic to hydrophilic composition and the inclusion of additional structural constraints, both of which decreased the polymer volume fraction in the swollen state. However, decreased mass release rates were at the expense of increased modulus and decreased lens flexibility. All lenses had high optical clarity (∼90% transmittance) and contained highly oxygen permeable siloxane composition similar to those found in commercial silicone hydrogel lenses, but they had poor flexibility for use as soft contact lenses.
Based on our results, the lenses described herein likely have too high of a modulus for use as extended-wear, soft contact lenses with drug release. Therefore, other controlled release methods would be better suited for maintaining adequate mechanical properties and achieving controlled and extended release for the duration of wear in soft, silicone hydrogel contact lens biomaterials. However, these biomaterials may find clinical use as more rigid gas permeable contact lenses or inserts.
改变硅水凝胶接触镜的组成和结构，实现地塞米松的控制释放，并评估与商业镜片相比的镜片光学和机械性能。由于大多数眼科药物是通过局部滴眼剂给药，其生物利用度和患者依从性都较低，因此从眼部生物材料中控制药物释放的需求非常大。
用不同的 PDMS/TRIS:DMA 比（0.25:1、0.67:1、1.5:1）以及额外的交联单体合成聚（PDMS-co-TRIS-co-DMA）接触镜。通过在微流控装置中以眼流量和大混合体积进行体外释放研究、在可见波长范围内进行光学质量研究、机械分析以及在溶胀状态下测定聚合物体积分数，对镜片进行了表征。
在体外眼流量下，通过延长和控制释放具有治疗相关浓度的地塞米松，实现了多日连续佩戴，最长可达 60 天。由于增加疏水性和亲水性组成以及包含额外结构约束的结合，导致释放延迟，这两者都降低了溶胀状态下的聚合物体积分数。然而，降低的质量释放速率是以增加的模量和降低的镜片柔韧性为代价的。所有镜片都具有高光学清晰度（约 90%的透光率），并且包含与商业硅水凝胶镜片相似的高透氧硅氧烷组成，但由于其柔韧性较差，不适合用作软性隐形眼镜。
根据我们的结果，本文所述的镜片由于模量过高，不太可能作为具有药物释放功能的延长佩戴时间的软性隐形眼镜使用。因此，其他控制释放方法可能更适合在软性硅水凝胶隐形眼镜生物材料中保持足够的机械性能，并实现控制和延长释放，以满足佩戴时间的需要。然而，这些生物材料可能会在更刚性的透气接触镜或插入物中找到临床应用。
