New and emerging roles for inhalational and direct antifungal drug delivery approaches for treatment of invasive fungal infections.

IF 4.2 2区 医学 Q1 INFECTIOUS DISEASES Expert Review of Anti-infective Therapy Pub Date : 2024-09-29 DOI:10.1080/14787210.2024.2409408
Chin Fen Neoh, Wirawan Jeong, David C M Kong, Justin Beardsley, Philip Chi Lip Kwok, Monica A Slavin, Sharon C-A Chen
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Abstract

Introduction: The rising prevalence of difficult-to-treat, deep-seated invasive fungal diseases (IFD) has led to high mortality. Currently available antifungal treatments, administered predominantly orally or intravenously, may not sufficiently penetrate certain body sites, and/or are associated with systemic toxicity. Little is known about how to position alternative administration approaches such as inhalational and direct drug delivery routes.

Areas covered: This review provides an updated overview of unconventional drug delivery strategies for managing IFD, focusing on inhalational (to target the lungs) and direct delivery methods to the central nervous system, bone/joint, and eyes. Novel compounds (e.g. opelconazole) and existing antifungals with innovative drug delivery systems currently undergoing clinical trials and/or used off-label in the clinical setting are discussed.

Expert opinion: For both inhalational agents and direct delivery approaches, there are similar challenges that include the absence of: approved formulations for specific administration routes, delivery vehicles that are simple and safe to use whilst maintaining potency and efficiency of delivery, animal models suitable for investigating pharmacokinetic/pharmacodynamic profiles of inhaled antifungals, and consensus on the composite endpoints and intervals for of follow-up in clinical trials. To meet these challenges, cooperation of all stakeholders in drug development and regulation is required.

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吸入式和直接抗真菌给药方法在治疗侵袭性真菌感染方面的新作用。
导言:难以治疗的深部侵袭性真菌病(IFD)发病率不断上升,导致死亡率居高不下。目前可用的抗真菌治疗方法主要通过口服或静脉注射,可能无法充分渗透某些身体部位,和/或与全身毒性有关。人们对如何定位吸入和直接给药途径等替代给药方法知之甚少:本综述对治疗 IFD 的非常规给药策略进行了最新概述,重点关注吸入(针对肺部)和直接给药到中枢神经系统、骨/关节和眼睛的方法。本文讨论了目前正在进行临床试验和/或在临床环境中标签外使用的新型化合物(如奥培康唑)和具有创新给药系统的现有抗真菌药物:对于吸入制剂和直接给药方法来说,都面临着类似的挑战,其中包括:缺乏针对特定给药途径的经批准的制剂;缺乏既简单安全又能保持药效和给药效率的给药载体;缺乏适合研究吸入抗真菌药物的药代动力学/药效学特征的动物模型;以及缺乏对临床试验中综合终点和随访间隔的共识。为了应对这些挑战,需要药物开发和监管方面的所有利益相关者通力合作。
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来源期刊
CiteScore
11.20
自引率
0.00%
发文量
66
审稿时长
4-8 weeks
期刊介绍: Expert Review of Anti-Infective Therapy (ISSN 1478-7210) provides expert reviews on therapeutics and diagnostics in the treatment of infectious disease. Coverage includes antibiotics, drug resistance, drug therapy, infectious disease medicine, antibacterial, antimicrobial, antifungal and antiviral approaches, and diagnostic tests.
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