Systemic delivery of tenofovir alafenamide using dissolving and implantable microneedle patches.
Systemic delivery of tenofovir alafenamide using dissolving and implantable microneedle patches.
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DOI：
10.1016/j.mtbio.2022.100217
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发表时间：
2022-01
期刊：
影响因子：
--
通讯作者：
Donnelly RF
中科院分区：
文献类型：
--
作者：
Paredes AJ;Volpe-Zanutto F;Vora LK;Tekko IA;Permana AD;Picco CJ;McCarthy HO;Donnelly RF
人类免疫缺陷病毒（HIV）仍然是全球健康问题，目前有3770万人感染该病毒，每年新增病例150万例。目前的抗逆转录病毒（ARV）疗法是通过口服途径每天给药，往往是终身治疗，导致药丸疲劳和治疗依从性差。因此，积极寻求使用替代途径施用ARV药物的新制剂的开发。从这个意义上说，微针阵列贴片（MAP）提供了一个独特的以用户为中心的平台，可以无痛地自我应用于皮肤并将药物输送到体循环。在这项工作中，溶解和植入的地图加载与替诺福韦艾拉酚胺（TAF）的开发与系统释放药物的目的。两种MAP均足够强以刺穿切除的新生全层猪皮并形成药物贮库。在透析膜模型中进行的体外释放实验表明，在所有情况下，药物的递送相对较快。Franz细胞实验显示，溶解型和植入型MAPs在皮肤中沉积的TAF分别为47.87 ± 16.33 μg和1208.04 ± 417.9 μg。大鼠药代动力学实验表明，TAF快速代谢为替诺福韦，代谢产物从血浆中快速消除。这项工作中描述的地图可以作为一种替代目前的口服治疗艾滋病毒管理。艾滋病毒仍然是全球关注的问题，目前有3 800万人感染艾滋病毒。抗逆转录病毒疗法可以防止艾滋病毒传播，延长感染者的预期寿命。MAPs构成了一个有吸引力的平台，用于提供抗逆转录病毒药物，包括TAF。获得溶解的和可植入的TAF MAP，并在体外和离体进行表征。两种MAP均能够在大鼠中全身递送TAF。
The human immunodeficiency virus (HIV) remains a global health concern, with 37.7 million people currently living with the infection and 1.5 million new cases every year. Current antiretroviral (ARV) therapies are administered through the oral route daily, often in lifelong treatments, leading to pill fatigue and poor treatment adherence. Therefore, the development of novel formulations for the administration ARV drugs using alternative routes is actively sought out. In this sense, microneedle array patches (MAPs) offer a unique user-centric platform that can be painlessly self-applied to the skin and deliver drugs to the systemic circulation. In this work, dissolving and implantable MAPs loaded with the tenofovir alafenamide (TAF) were developed with the aim of releasing the drug systemically. Both MAPs were sufficiently strong to pierce excised neonatal full-thickness porcine skin and form drug depots. In vitro release experiments performed in dialysis membrane models, demonstrated a relatively fast delivery of the drug in all cases. Franz cells experiments revealed that dissolving and implantable MAPs deposited 47.87 ± 16.33 μg and 1208.04 ± 417.9 μg of TAF in the skin after 24 h. Pharmacokinetic experiments in rats demonstrated a fast metabolization of TAF into tenofovir, with a rapid elimination of the metabolite from the plasma. The MAPs described in this work could be used as an alternative to current oral treatments for HIV management. HIV is still a global concern, with 38 million people currently living with the infection. ARV therapy can prevent HIV spread and extend life expectancy in infected people. MAPs constitute an attractive platform for the delivery of antiretroviral drugs including TAF. Dissolving and implantable TAF MAPs were obtained and characterised in vitro and ex vivo. Both MAPs were able to deliver TAF systemically in rats.
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影响因子：
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