Vora Lalitkumar K, Tekko Ismaiel A, Zanutto Fabiana Volpe, Sabri Akmal, Choy Robert K M, Mistilis Jessica, Kwarteng Priscilla, Jarrahian Courtney, McCarthy Helen O, Donnelly Ryan F
Medical Biology Centre, School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK.
PATH, 2201 Westlake Avenue, Seattle, DC 98121, USA.
Pharmaceutics. 2024 Jan 20;16(1):142. doi: 10.3390/pharmaceutics16010142.
Microarray patches (MAPs) have shown great potential for efficient and patient-friendly drug delivery through the skin; however, improving their delivery efficiency for long-acting drug release remains a significant challenge. This research provides an overview of novel strategies aimed at enhancing the efficiency of MAP delivery of micronized cabotegravir sodium (CAB Na) for HIV pre-exposure prophylaxis (PrEP). The refinement of microneedle design parameters, including needle length, shape, density, and arrangement, and the formulation properties, such as solubility, viscosity, polymer molecular weight, and stability, are crucial for improving penetration and release profiles. Additionally, a bilayer MAP optimization step was conducted by diluting the CAB Na polymeric mixture to localize the drug into the tips of the needles to enable rapid drug deposition into the skin following MAP application. Six MAP designs were analyzed and investigated with regard to delivery efficiency into the skin in ex vivo and in vivo studies. The improved MAP design and formulations were found to be robust and had more than 30% in vivo delivery efficiency, with plasma levels several-fold above the therapeutic concentration over a month. Repeated weekly dosing demonstrated the robustness of MAPs in delivering a consistent and sustained dose of CAB. In summary, CAB Na MAPs were able to deliver therapeutically relevant levels of drug.
微阵列贴片(MAPs)已显示出通过皮肤实现高效且对患者友好的药物递送的巨大潜力;然而,提高其长效药物释放的递送效率仍然是一项重大挑战。本研究概述了旨在提高微粉化卡博特韦钠(CAB Na)用于HIV暴露前预防(PrEP)的MAP递送效率的新策略。微针设计参数的优化,包括针长、形状、密度和排列,以及制剂性质,如溶解度、粘度、聚合物分子量和稳定性,对于改善渗透和释放特性至关重要。此外,通过稀释CAB Na聚合物混合物进行双层MAP优化步骤,以使药物定位在针尖,从而在MAP应用后能够将药物快速沉积到皮肤中。在体外和体内研究中,对六种MAP设计的皮肤递送效率进行了分析和研究。发现改进后的MAP设计和制剂具有良好的稳定性,体内递送效率超过30%,血浆水平在一个多月内比治疗浓度高出几倍。每周重复给药证明了MAPs在递送一致且持续剂量的CAB方面的稳定性。总之,CAB Na MAPs能够递送具有治疗相关性的药物水平。