Maliba Pharmacy College, Uka Tarsadia University, Surat 394350, India.
Maliba Pharmacy College, Uka Tarsadia University, Surat 394350, India.
Mater Sci Eng C Mater Biol Appl. 2020 Jul;112:110885. doi: 10.1016/j.msec.2020.110885. Epub 2020 Mar 23.
A fixed combination of bimatoprost/timolol eye drop solution is used to manage the elevated intra-ocular pressure in glaucoma patients, including individuals whose condition is poorly controlled by monotherapy. Eye drop solutions are generally given in high dose, due to poor ocular bioavailability. The high ocular dose of bimatoprost and timolol lead to hyperaemia and systemic cardiac side effects respectively. Here, we introduce multiple implant-laden contact lenses (IM) to passively deliver timolol, bimatoprost and hyaluronic acid at therapeutically relevant doses without high burst release. The drug-loaded implants were individually implanted in the outer periphery of the silicone contact lenses. Atomic force microscopy showed the smooth surface of the implant contact lens, as the implants were inside the contact lens matrix. The implant lens (IM) showed major loss of drugs [timolol = 60.60%, bimatoprost = 61.75% and HA = 46.03%] during the monomer extraction and wet sterilization, while the option of dry radiation sterilization (IM-R lens) and hydration for 24 h prior to use showed relatively lower loss of drugs [timolol = 16.87%, bimatoprost = 47.95% and HA = 24.41%]. The in-vitro drugs release data of IM-R lens, showed sustained release for 72 h, with low burst release in comparison to the soaked (SM) and direct drug-laden contact lenses (DL). The in vivo drug release data in the rabbit tear fluid showed sustained release using IM-R lens in comparison to the SM lens and eye drop therapy. The burst release with the IM-R lens was many folds reduced, which could bypass the side effects associated with multiple eye drop therapy. The in vivo pharmacodynamic study in the rabbit model showed peak and valley profile with multiple eye drop therapy, while IM-R lens showed prolong reduction in intra ocular pressure (IOP) for 120 h. The study demonstrates the application of implantation technology to deliver multiple drug through contact lenses to treat glaucoma.
一种比马前列素/噻吗洛尔固定组合滴眼溶液用于治疗青光眼患者的眼内压升高，包括那些单一疗法控制不佳的患者。由于眼部生物利用度差，滴眼溶液通常给予高剂量。比马前列素和噻吗洛尔的高眼部剂量分别导致充血和全身心脏副作用。在这里，我们引入了多个植入式隐形眼镜 (IM)，以被动递送至治疗相关剂量的噻吗洛尔、比马前列素和透明质酸，而不会出现高突释。药物负载的植入物分别植入硅酮隐形眼镜的外周边缘。原子力显微镜显示，由于植入物位于隐形眼镜基质内，植入式隐形眼镜的表面光滑。植入式隐形眼镜 (IM) 在单体提取和湿消毒过程中显示出主要的药物损失 [噻吗洛尔=60.60%，比马前列素=61.75%和 HA=46.03%]，而选择干辐射消毒 (IM-R 隐形眼镜) 和在使用前水化 24 小时显示出相对较低的药物损失 [噻吗洛尔=16.87%，比马前列素=47.95%和 HA=24.41%]。IM-R 隐形眼镜的体外药物释放数据显示，在 72 小时内持续释放，与浸泡 (SM) 和直接载药隐形眼镜 (DL) 相比，突释较低。与 SM 隐形眼镜和滴眼治疗相比，兔泪液中的体内药物释放数据显示 IM-R 隐形眼镜持续释放。与 IM-R 隐形眼镜相比，突释倍数降低，可避免与多次滴眼治疗相关的副作用。兔模型中的体内药效学研究表明，与多次滴眼治疗相比，出现峰值和谷值，而 IM-R 隐形眼镜显示眼压 (IOP) 延长 120 小时下降。该研究证明了植入技术在通过隐形眼镜递送至治疗青光眼的多种药物中的应用。
