Naser Yara A, Tekko Ismaiel A, Vora Lalitkumar K, Peng Ke, Anjani Qonita K, Greer Brett, Elliott Christopher, McCarthy Helen O, Donnelly Ryan F
School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK.
School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK; Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Aleppo University, Aleppo, Syria.
J Control Release. 2023 Apr;356:416-433. doi: 10.1016/j.jconrel.2023.03.003. Epub 2023 Mar 13.
Hydrogel-forming microarray patches (HF-MAPs) are used to circumvent the skin barrier and facilitate the noninvasive transdermal delivery of many hydrophilic substances. However, their use in the delivery of hydrophobic agents is a challenging task. This work demonstrates, for the first time, the successful transdermal long-acting delivery of the hydrophobic atorvastatin (ATR) via HF-MAPs using poly(ethylene)glycol (PEG)-based solid dispersion (SD) reservoirs. PEG-based SDs of ATR were able to completely dissolve within 90 s in vitro. Ex vivo results showed that 2.05 ± 0.23 mg of ATR/0.5 cm patch was delivered to the receiver compartment of Franz cells after 24 h. The in vivo study, conducted using Sprague Dawley rats, proved the versatility of HF-MAPs in delivering and maintaining therapeutically-relevant concentrations (> 20 ng·mL) of ATR over 14 days, following a single HF-MAP application for 24 h. The long-acting delivery of ATR suggests the successful formation of hydrophobic microdepots within the skin, allowing for the subsequent sustained delivery as they gradually dissolve over time, as shown in this work. When compared to the oral group, the use of the HF-MAP formulation improved the overall pharmacokinetics profile of ATR in plasma, where significantly higher AUC values resulting in ∼10-fold higher systemic exposure levels were obtained. This novel system offers a promising, minimally-invasive, long-acting alternative delivery system for ATR that is capable of enhancing patient compliance and therapeutic outcomes. It also proposes a unique promising platform for the long-acting transdermal delivery of other hydrophobic agents.
水凝胶形成微阵列贴片（HF-MAPs）用于绕过皮肤屏障，促进多种亲水性物质的非侵入性透皮递送。然而，将其用于递送疏水性药物是一项具有挑战性的任务。这项工作首次证明了使用基于聚乙二醇（PEG）的固体分散体（SD）储库，通过HF-MAPs成功实现了疏水性阿托伐他汀（ATR）的透皮长效递送。基于PEG的ATR固体分散体在体外90秒内能够完全溶解。体外实验结果表明，24小时后，2.05±0.23mg的ATR/0.5cm贴片被递送至Franz细胞的接受室。在Sprague Dawley大鼠上进行的体内研究证明，在单次HF-MAP给药24小时后，HF-MAPs在14天内递送并维持治疗相关浓度（>20ng·mL）的ATR具有多功能性。ATR的长效递送表明在皮肤内成功形成了疏水性微贮库，随着时间的推移它们逐渐溶解，从而实现随后的持续递送，如本研究所示。与口服组相比，使用HF-MAP制剂改善了血浆中ATR的整体药代动力学特征，获得了显著更高的AUC值，导致全身暴露水平提高约10倍。这种新型系统为ATR提供了一种有前景的、微创的、长效的替代递送系统，能够提高患者的依从性和治疗效果。它还为其他疏水性药物的长效透皮递送提出了一个独特的有前景的平台。
