Department of Pharmaceutical Chemistry and Quality Assurance, SVKM's Dr. Bhanuben Nanavati College of Pharmacy , Mumbai, Maharashtra, India.
Department of Quality Assurance, SVKM's Dr. Bhanuben Nanavati College of Pharmacy , Mumbai, Maharashtra, India.
Expert Opin Drug Deliv. 2020 Jul;17(7):903-918. doi: 10.1080/17425247.2020.1762565. Epub 2020 May 26.
Human immunodeficiency virus (HIV) targets and modulates the immune system increasing the risk of other associated infections. Highly active antiretroviral therapy (HAART) has significantly improved AIDS-associated morbidity, but has limitations of adverse effects, frequent dosing regimen leading to medical non-adherence. Drug delivery systems that target HIV reservoirs could potentially reduce dose-dependent toxicity and the duration of treatment. The major cellular HIV reservoirs are macrophages and CD4 T cells with macrophages being responsible for carrying and spreading the virus. The crucial involvement of macrophages in the pathogenesis of HIV infection has led to development of macrophage targeted nanocarrier delivery systems.
Eradication of viral reservoirs like HIV-infected macrophages has emerged to be a fundamental barrier and challenge for complete eradication of HIV from the immune system. Literature reports several macrophage targeted nanocarrier delivery systems developed as either functionalized or non-functionalized formulations such as liposomes, ethosomes, polymeric nanoparticles, dendrimers, and solid lipid nanoparticles showcasing superior efficacy over the conventional antiretroviral delivery systems.
The development of fixed dose combination of antiretroviral drugs into macrophage targeted delivery systems should factor in the inherent plasticity and heterogeneity of macrophages that is dependent on their microenvironment. A rational selection of nanocarriers will facilitate selectivity and enhanced efficacy of antiretroviral drugs accompanied by reduced dosing and toxicity. Such macrophage targeted delivery systems would positively impact the therapeutic outcomes in the management of HIV infection.
人类免疫缺陷病毒 (HIV) 会攻击并调节免疫系统，从而增加其他相关感染的风险。高效抗逆转录病毒疗法 (HAART) 显著改善了艾滋病相关发病率，但存在不良反应、频繁给药方案导致医疗不依从等局限性。针对 HIV 储存库的药物递送系统有可能降低剂量依赖性毒性和治疗持续时间。主要的细胞 HIV 储存库是巨噬细胞和 CD4 T 细胞，巨噬细胞负责携带和传播病毒。巨噬细胞在 HIV 感染发病机制中的关键作用导致了针对巨噬细胞的纳米载体药物递送系统的发展。
像 HIV 感染的巨噬细胞这样的病毒储存库的根除已成为从免疫系统中完全清除 HIV 的基本障碍和挑战。文献报道了几种作为功能化或非功能化制剂开发的巨噬细胞靶向纳米载体药物递送系统，例如脂质体、醇质体、聚合物纳米颗粒、树枝状大分子和固体脂质纳米颗粒，与传统抗逆转录病毒药物递送系统相比，具有更高的疗效。
将抗逆转录病毒药物的固定剂量组合开发成巨噬细胞靶向递送系统时，应考虑到巨噬细胞固有的可塑性和异质性，这取决于它们的微环境。纳米载体的合理选择将有助于提高抗逆转录病毒药物的选择性和疗效，同时减少剂量和毒性。这种针对巨噬细胞的药物递送系统将对 HIV 感染管理的治疗结果产生积极影响。
