Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Jhunjhunu, Rajasthan 333031, India.
Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Jhunjhunu, Rajasthan 333031, India.
J Control Release. 2020 Aug 10;324:379-404. doi: 10.1016/j.jconrel.2020.05.022. Epub 2020 May 24.
In spite of introduction of combination antiretroviral therapy (cART) against human immunodeficiency virus (HIV) infection; inaccessibility and poor adherence to oral cART costs 10 in 100,000 death worldwide. Failure in adherence leads to viral rebound, emergence of drug resistance and anticipated HIV infection in high risk individuals. Various Long-acting antiretroviral (LA ARV) nanoformulations including nano-prodrug, solid drug nanoparticles (SDN), nanocrystals, aspherical nanoparticles, polymeric and lipidic nanoparticles have shown plasma/tissue drug concentration in the therapeutic range for several weeks during pre-clinical evaluation. LA ARV nanoformulations therefore have replaced cART as better alternative for the treatment of HIV infection. Cabenuva™ is recently approved by Health Canada containing LA cabotegravir+LA rilpivirine nanocrystals (ViiV healthcare) for once monthly administration by intramuscular route. The LA nanoformulation due to its nanosize insist on better stability, delivery to lymphatic, slow release into systemic circulation via lymphatic-circulatory system conjoint and secondary drug depot within infiltered immune cells at site of administration and systemic circulation in contrast to conventional drugs. However, the pharmacokinetic, biodistribution and efficacy of LA nanoformulations hinge onto physicochemical properties of the drugs and route of administration. Therefore, current review emphasizes on these contradistinctive factors that affects the reproducibility, safety, efficacy and toxicity of LA anti-HIV nanoformulations. Moreover, it expatiates on application of profuse nanoformulations for long-acting effect with promising preclinical discoveries and two clinical leads. To add on, utilization of physiology-based and mechanism-based pharmacokinetic modelling and in vivo animal models which could lead to enhanced safety and efficacy of LA ARV nanoformulations in humans have been included.
尽管引入了针对人类免疫缺陷病毒（HIV）感染的联合抗逆转录病毒疗法（cART）；但由于口服 cART 的不可及性和低依从性，全球每 10 万人中仍有 10 人死亡。依从性差会导致病毒反弹、出现耐药性，并使高危人群预期感染 HIV。各种长效抗逆转录病毒（LA ARV）纳米制剂，包括纳米前药、固体药物纳米颗粒（SDN）、纳米晶体、非球形纳米颗粒、聚合物和脂质体纳米颗粒，在临床前评估中已显示出在几周内达到治疗范围内的血浆/组织药物浓度。因此，LA ARV 纳米制剂已取代 cART，成为治疗 HIV 感染的更好选择。Cabenuva™ 最近获得加拿大卫生部批准，含有 LA 卡替拉韦+LA 利匹韦林纳米晶体（ViiV healthcare），每月通过肌肉注射一次。由于其纳米尺寸，LA 纳米制剂坚持更好的稳定性，递送至淋巴系统，通过淋巴循环系统联合和注入的免疫细胞内的二级药物库缓慢释放到全身循环中，与传统药物相反。然而，LA 纳米制剂的药代动力学、生物分布和疗效取决于药物的理化性质和给药途径。因此，目前的综述强调了这些有区别的因素，这些因素影响 LA 抗 HIV 纳米制剂的重现性、安全性、疗效和毒性。此外，它阐述了大量纳米制剂在长效作用方面的应用，以及有前途的临床前发现和两个临床先导。此外，还包括基于生理学和基于机制的药代动力学建模以及体内动物模型的应用，这可能会提高 LA ARV 纳米制剂在人体中的安全性和疗效。
