School of Pharmacy, University of the Western Cape, Robert Sobukwe Road, Bellville 7535, South Africa.
Department of Pharmacotherapy, Washington State University, College of Pharmacy and Pharmaceutical Sciences, Yakima, WA 98901, United States.
Biomed Pharmacother. 2022 Jul;151:113189. doi: 10.1016/j.biopha.2022.113189. Epub 2022 May 28.
Tuberculosis (TB) and human immunodeficiency virus (HIV) represent a significant burden of disease on a global scale. Despite improvements in the global epidemic status, largely facilitated by increased access to pharmacotherapeutic interventions, slow progress in the development of new clinical interventions coupled with growing antimicrobial resistance to existing therapies represents a global health crisis. There is an urgent need to expand the armamentarium of TB and HIV therapeutic strategies. Host mediated immune responses represent an untapped reservoir of novel approaches for TB and HIV. Antimicrobial peptides (AMPs) are an essential aspect of the immune system. Cathelicidins and defensins AMPs have been studied for their potential applications in TB and HIV therapeutic interventions. Genetic polymorphism across different population groups may affect endogenous expression or activity of AMPs, potentially influencing therapeutic outcomes. However, certain genetic polymorphisms in autophagy pathways may alter the downstream effects of nano-delivery of cathelicidin. On the other hand, certain genetic polymorphisms in beta-defensins may provide a protective role in reducing HIV-1 mother-to-child-transmission. Pharmaceutical development of cathelicidins and defensins is disadvantaged with complex challenges. Nanoparticle formulations improve pharmacokinetics and biocompatibility while facilitating targeted drug delivery, potentially minimising the risk of immunogenicity or non-specific haemolytic activity. This review aims to explore the potential viability of using cathelicidins and defensins as novel pharmacotherapy in the management of TB and HIV, highlight potential pharmacogenomic implications in host mediated immunity and AMP therapeutic applications, as well as propose novel drug delivery strategies represented by nanomedicine for AMPs.
结核病 (TB) 和人类免疫缺陷病毒 (HIV) 在全球范围内都构成了重大疾病负担。尽管由于获得更多的药物治疗干预措施而使全球流行状况得到改善，但新的临床干预措施的开发进展缓慢，加上现有治疗方法的抗微生物耐药性不断增强，这构成了一个全球卫生危机。迫切需要扩大结核病和 HIV 治疗策略的手段。宿主介导的免疫反应代表了结核病和 HIV 的新方法的未开发资源。抗菌肽 (AMPs) 是免疫系统的重要组成部分。抗菌肽 cathelicidins 和 defensins 已被研究用于结核病和 HIV 治疗干预措施的潜在应用。不同人群群体中的遗传多态性可能会影响 AMPs 的内源性表达或活性，从而可能影响治疗结果。然而，自噬途径中的某些遗传多态性可能会改变 cathelicidin 纳米递药的下游效应。另一方面，β-防御素中的某些遗传多态性可能在降低 HIV-1 母婴传播方面提供保护作用。抗菌肽的药物开发面临着复杂的挑战，处于劣势地位。纳米颗粒制剂可改善药代动力学和生物相容性，同时促进靶向药物递送，从而最大程度地降低免疫原性或非特异性溶血活性的风险。本综述旨在探讨抗菌肽和防御素作为结核病和 HIV 管理中新型药物治疗的潜在可行性，强调宿主介导的免疫和 AMP 治疗应用中潜在的药物基因组学意义，并提出代表 AMP 纳米医学的新型药物递送策略。
