Naser Yara A, Vora Lalitkumar K, Tekko Ismaiel A, Peng Ke, Volpe-Zanutto Fabiana, Greer Brett, Paredes Alejandro, McCarthy Helen O, Donnelly Ryan F
School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, U.K.
Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Aleppo University, Aleppo 00 963, Syria.
ACS Appl Mater Interfaces. 2024 Oct 2;16(41):55027-44. doi: 10.1021/acsami.4c05517.
The increasing popularity of prolonged-release dosage forms, owing to their ability to provide continuous drug release after administration, has significantly improved patient compliance and overall quality of life. However, achieving prolonged release beyond 24 h frequently requires the use of invasive methods, including injections or implants, which may prove challenging for people suffering from needle phobia. This study introduces atorvastatin (ATR) microparticles (MPs) or nanocrystal (NCs) dissolving microarray patches (D-MAPs) as a noninvasive alternative for intradermal drug delivery over a two-week period for the management of hyperlipidemia. The MP-loaded D-MAPs exhibited an average drug loading of 5.15 ± 0.4 mg of ATR per patch, surpassing the 2.4 ± 0.11 mg/patch observed with NC-loaded D-MAPs. Skin deposition studies demonstrated the superior performance of MP D-MAPs, which delivered 2.0 ± 0.33 mg of ATR per 0.75 cm patch within 24 h, representing 38.76% of the initial amount of drug loaded. In contrast, NC D-MAPs delivered approximately 0.89 ± 0.12 mg of ATR per 0.75 cm patch at 24 h, equivalent to 38.42 ± 5.13% of the initial ATR loaded. Due to their favorable results, MP D-MAPs were chosen for an study using Sprague-Dawley rats. The findings demonstrated the capacity of D-MAPs to deliver and attain therapeutically relevant ATR concentrations (>20 ng/mL) for 14 days after a single 24-h application. This study is the first to successfully demonstrate the long-acting transdermal delivery of ATR using MP-loaded D-MAPs after a 24-h single-dose application. The innovative D-MAP system, particularly when loaded with MP, arises as a promising, minimally invasive, long-acting substitute for ATR delivery. This technology has the potential to improve patient compliance and therapeutic outcomes while also significantly advancing the field of transdermal drug delivery.
由于能够在给药后提供持续的药物释放，缓释剂型越来越受欢迎，这显著提高了患者的依从性和整体生活质量。然而，要实现超过24小时的缓释通常需要使用侵入性方法，包括注射或植入，这对患有针头恐惧症的人来说可能具有挑战性。本研究介绍了阿托伐他汀（ATR）微粒（MPs）或纳米晶体（NCs）溶解微阵列贴片（D-MAPs），作为一种非侵入性替代方法，用于在两周内进行皮内给药以治疗高脂血症。负载MP的D-MAPs平均每片的ATR载药量为5.15±0.4毫克，超过了负载NC的D-MAPs所观察到的2.4±0.11毫克/片。皮肤沉积研究证明了MP D-MAPs的优越性能，其在24小时内每0.75平方厘米贴片递送2.0±0.33毫克的ATR，占初始载药量的38.76%。相比之下，NC D-MAPs在24小时时每0.75平方厘米贴片递送约0.89±0.12毫克的ATR，相当于初始负载ATR的38.42±5.13%。由于其良好的结果，MP D-MAPs被选用于一项使用Sprague-Dawley大鼠的研究。研究结果表明，D-MAPs在单次24小时给药后能够在14天内递送并达到治疗相关的ATR浓度（>20纳克/毫升）。本研究首次成功证明了在单次24小时给药后，使用负载MP的D-MAPs实现了ATR的长效透皮递送。创新的D-MAP系统，特别是当负载MP时，成为一种有前途的、微创的、长效的ATR递送替代方法。这项技术有可能提高患者的依从性和治疗效果，同时也显著推动透皮给药领域的发展。
