Tieppo Arianna, Boggs Aarika C, Pourjavad Payam, Byrne Mark E
Biomimetic & Biohybrid Materials, Biomedical Devices, & Drug Delivery Laboratories, Department of Chemical Engineering, Auburn University, Auburn, AL 36849-5127, USA.
Biomimetic & Biohybrid Materials, Biomedical Devices, & Drug Delivery Laboratories, Department of Chemical Engineering, Auburn University, Auburn, AL 36849-5127, USA; NSF REU Site in Micro-Nano Structured Materials, Therapeutics, and Devices, Auburn University, Auburn, AL 36849-5127, USA.
Cont Lens Anterior Eye. 2014 Aug;37(4):305-13. doi: 10.1016/j.clae.2014.04.005. Epub 2014 Jun 2.
Several methods have been proposed to achieve an extended and controlled release of ocular therapeutics via contact lenses; however, the experimental conditions used to study the drug release vary greatly and significantly influence the release kinetics. In this paper, we examine variations in the release conditions and their effect on the release of both hydrophilic and hydrophobic drugs (ketotifen fumarate, diclofenac sodium, timolol maleate and dexamethasone) from conventional hydrogel and silicone hydrogel lenses. Drug release was studied under different conditions, varying volume, mixing rates, and temperature. Volume had the biggest effect on the release profile, which ironically is the least consistent variable throughout the literature. When a small volume (2-30 mL) was used with no forced mixing and solvent exchange every 24 h, equilibrium was reached promptly much earlier than solvent exchange, significantly damping the drug release rate and artificially extending the release duration, leading to false conclusions. Using a large volume (200-400 mL) with a 30 rpm mixing rate and no solvent exchange, the release rate and total mass released was significantly increased. In general, the release performed in small volumes with no force mixing exhibited cumulative mass release amounts of 3-12 times less than the cumulative release amounts in large volumes with mixing. Increases in mixing rate and temperature resulted in relatively small increases of 1.4 and 1.2 times, respectively in fractional mass released. These results strongly demonstrate the necessity of proper and thorough analysis of release data to assure that equilibrium is not affecting release kinetics. This is paramount for comparison of various controlled drug release methods of therapeutic contact lenses, validation of the potential of lenses as an efficient and effective means of drug delivery, as well as increasing the likelihood of only the most promising methods reaching in vivo studies.
已经提出了几种通过隐形眼镜实现眼部治疗药物延长释放和控释的方法；然而，用于研究药物释放的实验条件差异很大，并且对释放动力学有显著影响。在本文中，我们研究了释放条件的变化及其对亲水性和疏水性药物（富马酸酮替芬、双氯芬酸钠、马来酸噻吗洛尔和地塞米松）从传统水凝胶和硅水凝胶镜片中释放的影响。在不同条件下研究了药物释放，包括不同体积、混合速率和温度。体积对释放曲线的影响最大，具有讽刺意味的是，这是整个文献中最不一致的变量。当使用小体积（2 - 30 mL）且不进行强制混合且每24小时不进行溶剂交换时，比溶剂交换更早地迅速达到平衡，显著抑制了药物释放速率并人为延长了释放持续时间，从而导致错误结论。使用大体积（200 - 400 mL）、30 rpm的混合速率且不进行溶剂交换时，释放速率和释放的总质量显著增加。一般来说，在不进行强制混合的小体积中进行的释放，其累积质量释放量比在有混合的大体积中的累积释放量少3 - 12倍。混合速率和温度的增加分别导致释放的分数质量相对较小地增加1.4倍和1.2倍。这些结果有力地证明了对释放数据进行适当和全面分析的必要性，以确保平衡不会影响释放动力学。这对于比较治疗性隐形眼镜的各种控释方法、验证隐形眼镜作为一种高效药物递送手段的潜力以及增加只有最有前景的方法进入体内研究的可能性至关重要。
