Biomimetic & Biohybrid Materials, Biomedical Devices, & Drug Delivery Laboratories, Department of Chemical Engineering, Auburn University, Auburn, AL 36849-5127, USA.
J Control Release. 2012 Feb 10;157(3):391-7. doi: 10.1016/j.jconrel.2011.09.087. Epub 2011 Oct 1.
In this paper, we demonstrate the successful in vivo extended release of a small molecular weight therapeutic, ketotifen fumarate (MW=425), from molecularly imprinted, therapeutic contact lenses. This is the first time that a steady, effective concentration of drug is maintained in the tear film from a contact lens for an extended period of time for the entire duration of lens wear. Poly(HEMA-co-AA-co-AM-co-NVP-co-PEG200DMA) soft contact lenses were prepared (100±5 μm thickness, diameter 11.8 mm, power zero), and a constant tear film concentration of 170±30 μg/mL was measured for up to 26 hrs in a New Zealand white rabbit model. The results showed a dramatic increase in ketotifen mean residence time (MRT) and bioavailability compared to topical drop therapy and drug soaked lenses. The MRT for imprinted lenses was 12.47±3.99 hrs, ~4 and 50 fold greater than non-imprinted lenses and 0.035% eye drops (Zaditor®), respectively. Furthermore, AUC(0-26 hrs) was 9 and 94 fold greater for imprinted lenses than non-imprinted lenses and eye drops, respectively. The results indicate that molecular imprinting provides an exciting rational engineering strategy for sustained release. It is clear that imprinted lenses are very promising combination devices and are much more effective and efficient delivery devices than eye drops.
在本文中，我们展示了从小分子治疗药物富马酸酮替芬（MW=425）的分子印迹治疗隐形眼镜中成功实现体内延长释放。这是第一次从隐形眼镜中在整个镜片佩戴期间将稳定、有效的药物浓度维持在泪膜中延长时间。制备了聚（HEMA-co-AA-co-AM-co-NVP-co-PEG200DMA）软性隐形眼镜（厚度 100±5 μm，直径 11.8 mm，屈光度为零），并在新西兰白兔模型中测量了长达 26 小时的稳定泪膜浓度为 170±30 μg/mL。结果表明，与局部滴眼治疗和药物浸泡镜片相比，酮替芬的平均驻留时间（MRT）和生物利用度有了显著提高。印迹镜片的 MRT 为 12.47±3.99 小时，比非印迹镜片和 0.035%滴眼剂（Zaditor®）分别高 4 倍和 50 倍。此外，印迹镜片的 AUC（0-26 小时）分别是非印迹镜片和滴眼剂的 9 倍和 94 倍。结果表明，分子印迹为持续释放提供了一种令人兴奋的合理工程策略。很明显，印迹镜片是很有前途的组合装置，比滴眼剂更有效和高效。
