Design, formulation and evaluation of novel dissolving microarray patches containing a long-acting rilpivirine nanosuspension.
Design, formulation and evaluation of novel dissolving microarray patches containing a long-acting rilpivirine nanosuspension.
复制标题
DOI：
10.1016/j.jconrel.2018.11.002
复制
发表时间：
2018-12-28
期刊：
影响因子：
--
通讯作者：
Donnelly RF
中科院分区：
文献类型：
--
作者：
Mc Crudden MTC;Larrañeta E;Clark A;Jarrahian C;Rein-Weston A;Lachau-Durand S;Niemeijer N;Williams P;Haeck C;McCarthy HO;Zehrung D;Donnelly RF
抗击人类免疫缺陷病毒(HIV)传播的一种手段是提供长效、抗逆转录病毒(ARV)药物用于预防和治疗。开发一种谨慎的、自我管理和自我禁用的递送工具来递送这种抗逆转录病毒药物可以避免日常口服疗法的依从性问题。发展中的替代方案，如长效肌肉注射(IM)，需要定期进入卫生保健设施和利器处置设施。因此，开展了这项概念验证研究，以评估含有候选ARV药物利培韦林(RPV)的长效(LA)纳米悬浮的溶解微阵列贴片(MAP)的使用。MAP的机械强度很高，在体外可以穿透皮肤，在皮内传递RPV。在活体研究中，大鼠的RPV平均血浆浓度(在第7天的时间点为431 ng/ml)大约是先前临床研究中单剂后观察到的谷浓度的10倍。这些结果首次表明，通过确定IM和MAP给药之间的相对暴露，更大的多阵列溶解MAP可能潜在地用于有效地传递人体剂量的RPVLA。重要的是，在淋巴结中也检测到RPV，这表明这种ARV试剂有可能在较长时间内将这种ARV病毒传递到HIV复制的主要部位之一。这些地图可能会提高患者的接受度和对艾滋病毒预防和治疗方案的遵守，并与针刺伤害和血液传播疾病的情况作斗争，这将产生深远的好处，特别是对发展中国家的人来说。
One means of combating the spread of human immunodeficiency virus (HIV) is through the delivery of long-acting, antiretroviral (ARV) drugs for prevention and treatment. The development of a discreet, self-administered and self-disabling delivery vehicle to deliver such ARV drugs could obviate compliance issues with daily oral regimens. Alternatives in development, such as long-acting intramuscular (IM) injections, require regular access to health care facilities and disposal facilities for sharps. Consequently, this proof of concept study was developed to evaluate the use of dissolving microarray patches (MAPs) containing a long-acting (LA) nanosuspension of the candidate ARV drug, rilpivirine (RPV). MAPs were mechanically strong and penetrated skin in vitro, delivering RPV intradermally. In in vivo studies, the mean plasma concentration of RPV in rats (431 ng/ml at the Day 7 time point) was approximately ten-fold greater than the trough concentration observed after a single-dose in previous clinical studies. These results are the first to indicate, by the determination of relative exposures between IM and MAP administration, that larger multi-array dissolving MAPs could potentially be used to effectively deliver human doses of RPV LA. Importantly, RPV was also detected in the lymph nodes, indicating the potential to deliver this ARV agent into one of the primary sites of HIV replication over extended durations. These MAPs could potentially improve patient acceptability and adherence to HIV prevention and treatment regimens and combat instances of needle-stick injury and the transmission of blood-borne diseases, which would have far-reaching benefits, particularly to those in the developing world.
登录
查看更多内容
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：
1.1
作者：
Goel, Varun;Kumar, Dinesh;Singh, Sarman
通讯作者：
Singh, Sarman
影响因子：
4.9
作者：
Liu, Shu;Wu, Dan;Yamamoto, Akira
通讯作者：
Yamamoto, Akira
影响因子：
4.9
作者：
Azijn, Hilde;Tirry, Ilse;Rimsky, Laurence T.
通讯作者：
Rimsky, Laurence T.
影响因子：
7.3
作者：
Janssen, PAJ;Lewi, PJ;Stoffels, P
通讯作者：
Stoffels, P