Kim Ho-Joong, Zhang Kangyi, Moore Laura, Ho Dean
Department of Biomedical Engineering, Northwestern University , Evanston, Illinois 60208, United States.
ACS Nano. 2014 Mar 25;8(3):2998-3005. doi: 10.1021/nn5002968. Epub 2014 Feb 12.
Temporarily implanted devices, such as drug-loaded contact lenses, are emerging as the preferred treatment method for ocular diseases like glaucoma. Localizing the delivery of glaucoma drugs, such as timolol maleate (TM), can minimize adverse effects caused by systemic administration. Although eye drops and drug-soaked lenses allow for local treatment, their utility is limited by burst release and a lack of sustained therapeutic delivery. Additionally, wet transportation and storage of drug-soaked lenses result in drug loss due to elution from the lenses. Here we present a nanodiamond (ND)-embedded contact lens capable of lysozyme-triggered release of TM for sustained therapy. We find that ND-embedded lenses composed of enzyme-cleavable polymers allow for controlled and sustained release of TM in the presence of lysozyme. Retention of drug activity is verified in primary human trabecular meshwork cells. These results demonstrate the translational potential of an ND-embedded lens capable of drug sequestration and enzyme activation.
临时植入装置,如载药隐形眼镜,正成为青光眼等眼部疾病的首选治疗方法。定位青光眼药物(如马来酸噻吗洛尔,TM)的递送可以将全身给药引起的不良反应降至最低。尽管眼药水和药物浸泡的镜片可实现局部治疗,但其效用受到突释和缺乏持续治疗递送的限制。此外,药物浸泡镜片的湿态运输和储存会因药物从镜片中洗脱而导致药物损失。在此,我们展示了一种能够实现溶菌酶触发TM释放以进行持续治疗的纳米金刚石(ND)嵌入隐形眼镜。我们发现,由可酶切聚合物组成的ND嵌入镜片在溶菌酶存在的情况下能够实现TM的可控和持续释放。在原代人小梁网细胞中验证了药物活性的保留。这些结果证明了具有药物螯合和酶激活能力的ND嵌入镜片的转化潜力。