Development and Evaluation of Dissolving Microarray Patches for Co-administered and Repeated Intradermal Delivery of Long-acting Rilpivirine and Cabotegravir Nanosuspensions for Paediatric HIV Antiretroviral Therapy.
Development and Evaluation of Dissolving Microarray Patches for Co-administered and Repeated Intradermal Delivery of Long-acting Rilpivirine and Cabotegravir Nanosuspensions for Paediatric HIV Antiretroviral Therapy.
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DOI：
10.1007/s11095-022-03408-6
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发表时间：
2023-07
影响因子：
3.7
通讯作者：
Donnelly RF
中科院分区：
文献类型：
--
作者：
Moffatt K;Tekko IA;Vora L;Volpe-Zanutto F;Hutton ARJ;Mistilis J;Jarrahian C;Akhavein N;Weber AD;McCarthy HO;Donnelly RF
虽然在战胜 HIV 感染方面已经取得了重大进展，但抗逆转录病毒 (ARV) 治疗在儿科人群中的疗效往往因依从性差而受到阻碍。目前，利匹韦林 (RPV) 和卡博特韦 (CAB) 的两种长效 (LA) 肌内注射纳米混悬剂正在针对儿科人群进行临床开发。然而，管理需要获得医疗资源，是痛苦的，并且可能导致最终用户被针刺伤。为了克服这些障碍，开展了这项概念验证研究，以评估通过自失能溶解微阵列贴片 (MAP) 进行的 RPV LA 和 CAB LA 的皮内递送。配制了两种构象的可溶性 MAP，即传统的金字塔形和双层设计，并将 RPV 和 CAB 的各种纳米悬浮液纳入各自的 MAP 基质中。 MAP 具有机械强度，能够穿透离体皮肤并在皮内沉积 ARV。在大鼠体内的单剂量研究中，所有 ARV MAP 均表现出持续释放特性，且 RPV 和 CAB 的治疗相关血浆浓度分别检测到至少 63 和 28 天。在一项多剂量体内研究中，以 14 天的间隔重复使用 MAP，在整个研究期间维持了治疗相关的血浆浓度。这些结果说明了该平台重复维持 RPV 和 CAB 血浆浓度的潜力。因此，这些 MAP 可能是提高儿科人群依从性的一种可行选择，能够在患者舒适的家中以每两周一次或更少的频率无痛地进行给药。
Whilst significant progress has been made to defeat HIV infection, the efficacy of antiretroviral (ARV) therapy in the paediatric population is often hindered by poor adherence. Currently, two long-acting (LA) intramuscular injectable nanosuspensions of rilpivirine (RPV) and cabotegravir (CAB) are in clinical development for paediatric populations. However, administration requires access to healthcare resources, is painful, and can result in needle-stick injuries to the end user. To overcome these barriers, this proof-of-concept study was developed to evaluate the intradermal delivery of RPV LA and CAB LA via self-disabling dissolving microarray patches (MAPs). Dissolving MAPs of two conformations, a conventional pyramidal and a bilayer design, were formulated, with various nanosuspensions of RPV and CAB incorporated within the respective MAP matrix. MAPs were mechanically robust and were capable of penetrating ex vivo skin with intradermal ARV deposition. In a single-dose in vivo study in rats, all ARV MAPs demonstrated sustained release profiles, with therapeutically relevant plasma concentrations of RPV and CAB detected to at least 63 and 28 d, respectively. In a multi-dose in vivo study, repeated MAP applications at 14-d intervals maintained therapeutically relevant plasma concentrations throughout the duration of the study. These results illustrate the potential of the platform to repeatedly maintain plasma concentrations for RPV and CAB. As such, these MAPs could represent a viable option to improve adherence in the paediatric population, one that is capable of being painlessly administered in the comfort of the patient’s own home on a biweekly or less frequent basis.
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影响因子：
5.4
作者：
Moffatt K;Quinn C;McCague PJ;Donnelly RF
通讯作者：
Donnelly RF
DOI：
10.1016/j.jconrel.2017.07.032
发表时间：
2017-11-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
González-Vázquez P;Larrañeta E;McCrudden MTC;Jarrahian C;Rein-Weston A;Quintanar-Solares M;Zehrung D;McCarthy H;Courtenay AJ;Donnelly RF
通讯作者：
Donnelly RF
影响因子：
3.8
作者：
Bangsberg, DR;Perry, S;Moss, A
通讯作者：
Moss, A
影响因子：
1.1
作者：
Goel, Varun;Kumar, Dinesh;Singh, Sarman
通讯作者：
Singh, Sarman
影响因子：
3.9
作者：
Larson, B. J.;Gillmor, S. D.;Lagally, M. G.
通讯作者：
Lagally, M. G.