Varela-Garcia Angela, Gomez-Amoza José Luis, Concheiro Angel, Alvarez-Lorenzo Carmen
Departamento de Farmacología, Farmacia y Tecnología Farmacéutica, I+D Farma Group, Facultad de Farmacia and Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
Polymers (Basel). 2020 Sep 4;12(9):2026. doi: 10.3390/polym12092026.
A variety of ocular diseases are caused by viruses, and most treatments rely on the use of systemic formulations and eye drops. The efficient ocular barriers that oppose antiviral drug penetration have prompted the development of improved topical delivery platforms. The aim was to design hydrogel contact lenses endowed with an affinity for acyclovir (ACV) and its prodrug valacyclovir (VACV), first-choice drugs against herpes simplex virus (HSV) ocular keratitis, and that can sustain the release of therapeutic doses during daily wearing. Functional monomers suitable for interaction with these drugs were screened using computational modeling. Imprinted and non-imprinted hydrogels were prepared with various contents in the functional monomer methacrylic acid (MAA) and characterized in terms of swelling, transmittance, mechanical properties, and ocular compatibility (hen's egg test on chorioallantoic membrane (HET-CAM) assay). The values were in the range typical of soft contact lenses. Compared to ACV, the capability to load VACV was remarkably higher due to stronger electrostatic interactions with MAA. The advantages of the imprinting technology were evidenced for VACV. Stability of VACV loading solution/hydrogels under steam heat sterilization and subsequent drug release was investigated. Permeability studies through bovine and porcine cornea and sclera of the drug released from the hydrogels revealed that VACV accumulates in the cornea and can easily cross the sclera, which may facilitate the treatment of both anterior and posterior eye segments diseases.
多种眼部疾病由病毒引起,大多数治疗方法依赖于全身制剂和眼药水的使用。阻碍抗病毒药物渗透的有效眼部屏障促使人们开发改进的局部给药平台。目的是设计对阿昔洛韦(ACV)及其前药伐昔洛韦(VACV)具有亲和力的水凝胶隐形眼镜,这两种药物是治疗单纯疱疹病毒(HSV)性角膜炎的首选药物,并且在日常佩戴期间能够持续释放治疗剂量。使用计算模型筛选适合与这些药物相互作用的功能单体。用不同含量的功能单体甲基丙烯酸(MAA)制备了印迹和非印迹水凝胶,并对其溶胀、透光率、机械性能和眼部相容性(鸡胚绒毛尿囊膜试验(HET-CAM))进行了表征。这些值在软性隐形眼镜的典型范围内。与ACV相比,由于与MAA的静电相互作用更强,装载VACV的能力明显更高。印迹技术对VACV的优势得到了证明。研究了VACV装载溶液/水凝胶在蒸汽热灭菌下的稳定性以及随后的药物释放情况。通过水凝胶释放的药物对牛和猪角膜及巩膜的渗透性研究表明,VACV在角膜中蓄积并且可以很容易地穿过巩膜,这可能有助于治疗眼前节和眼后节疾病。