School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
Physiological Research Laboratory, Georgia Institute of Technology, Atlanta, GA 30332, USA.
J Control Release. 2019 May 10;301:140-145. doi: 10.1016/j.jconrel.2019.03.011. Epub 2019 Mar 12.
Lack of adherence to medication dosing schedules is a significant cause of morbidity and mortality with large associated financial costs. This is especially true for contraceptive hormones, which provide almost perfect prevention of pregnancy when used correctly, but have significant failure rates in typical use, due largely to poor adherence. To increase medication acceptability and adherence, we introduce pharmaceutical jewelry, in which a transdermal patch is incorporated into jewelry worn on skin. To demonstrate the approach, we incorporated transdermal patches containing the contraceptive hormone levonorgestrel (LNG) into an earring, a ring, a necklace, and a wrist watch. Transdermal delivery of LNG from earring patches across porcine skin ex vivo achieved a steady state flux of 1.7 μg/cm·h. Pharmacokinetic analysis in hairless rats yielded LNG delivery rates that maintained serum LNG levels near 1500 pg/ml throughout the 1-week patch application period, which is well above the human contraceptive threshold concentration of 200 pg/ml. When patches were applied cyclically for 16 h on and 8 h off to simulate earring removal at night, serum LNG concentrations dipped during off periods, but remained well above the human contraceptive threshold. Earring patches were well tolerated by the rats. We conclude that pharmaceutical jewelry can provide a novel method of drug delivery, especially for contraceptive hormones, that has the potential to improve acceptability and increase medication adherence.
不遵守药物剂量方案是导致发病率和死亡率的一个重要原因，同时还伴随着巨大的经济成本。这在避孕激素方面尤其如此，当正确使用时，避孕激素几乎可以达到完美的避孕效果，但在典型使用中却有很高的失败率，这主要是由于依从性差。为了提高药物的可接受性和依从性，我们引入了药物首饰，即将透皮贴片整合到佩戴在皮肤上的首饰中。为了展示这种方法，我们将含有避孕激素左炔诺孕酮（LNG）的透皮贴片整合到耳环、戒指、项链和手表中。将耳环贴片中的 LNG 经皮传递到猪皮的体外实验中，实现了 1.7μg/cm·h 的稳定通量。在无毛大鼠中的药代动力学分析得出，LNG 的释放率可以在 1 周的贴片应用期内将血清 LNG 水平维持在接近 1500pg/ml，远高于人类避孕的阈值浓度 200pg/ml。当贴片以 16 小时 ON 和 8 小时 OFF 的方式周期性应用，以模拟晚上取下耳环，在 OFF 期间，血清 LNG 浓度会下降，但仍远高于人类避孕的阈值。大鼠对耳环贴片的耐受性良好。我们得出结论，药物首饰可以提供一种新的药物输送方法，特别是对于避孕激素，这有可能提高药物的可接受性和增加用药依从性。
