Ali Maryam, Byrne Mark E
Biomimetic & Biohybrid Materials, Biomedical Devices, and Drug Delivery Laboratories, Department of Chemical Engineering, Auburn University, Auburn, AL, 36849, USA.
Pharm Res. 2009 Mar;26(3):714-26. doi: 10.1007/s11095-008-9818-6. Epub 2009 Jan 21.
Current dry eye treatment includes delivering comfort agents to the eye via drops, but low bioavailability and multiple administration continues to be a barrier to effective treatment. There exists a significant unmet need for devices to treat dry eye and for more comfortable contact lenses.
Using molecular imprinting strategies with an analysis of biology, we have rationally designed and synthesized hydrogel contact lenses that can release hyaluronic acid (HA) at a controlled rate.
Delayed release characteristics were significantly improved through biomimetic imprinting, as multiple functional monomers provided non-covalent complexation points within nelfilcon A gels without altering structural, mechanical, or optical properties. The diffusion coefficient of 1.2 million Dalton HA was controlled by varying the number and variety of functional monomers (increasing the variety lowered the HA diffusion coefficient 1.5 times more than single functional monomers, and 1.6 times more than nelfilcon A alone).
HA can be delivered from a daily disposable lens at a therapeutic rate of approximately 6 microg/h for 24 h. This is the first demonstration of imprinting a large molecular weight polymer within a hydrogel and the effect of imprinting on the reptation of the long chain macromolecule from the structure.
目前干眼症的治疗方法包括通过滴眼液向眼睛输送舒缓剂,但生物利用度低和需多次给药仍然是有效治疗的障碍。对于治疗干眼症的装置和更舒适的隐形眼镜,存在着尚未满足的重大需求。
通过分子印迹策略并结合生物学分析,我们合理设计并合成了能够以可控速率释放透明质酸(HA)的水凝胶隐形眼镜。
通过仿生印迹显著改善了缓释特性,因为多种功能单体在奈非那酮A凝胶内提供了非共价络合点,而不会改变其结构、机械或光学性能。通过改变功能单体的数量和种类来控制120万道尔顿HA的扩散系数(功能单体种类增加时,HA扩散系数降低的幅度比单一功能单体多1.5倍,比单独的奈非那酮A多1.6倍)。
HA可以从日抛型隐形眼镜中以约6微克/小时的治疗速率释放24小时。这是首次证明在水凝胶中印迹高分子量聚合物以及印迹对长链大分子从该结构中蠕动的影响。