Unlocking the potential of remdesivir: innovative approaches to drug delivery

Abstract

Given the recurrent waves of COVID-19 and the emergence of new viral infections, optimizing the potential of remdesivir as an antiviral agent is critical. While several reviews have explored the efficacy of remdesivir, few have comprehensively addressed its challenges, such as the necessity for intravenous infusion, suboptimal lung accumulation, and safety concerns related to its formulation. This review critically examines these challenges while proposing innovative solutions and effective combinations with other antiviral agents and repurposed drugs. By highlighting the role of complex generics, we aim to enhance therapeutic efficacy in ways not previously discussed in existing literature. Furthermore, we address the development of novel drug delivery systems which specifically aim to improve remdesivir’s pharmacological profile. By analyzing recent findings, we assess both the successes and limitations of current approaches, providing insights into ongoing challenges and strategies for further optimization. This review uniquely focuses on targeted drug delivery systems and innovative formulations, thereby maximizing remdesivir’s therapeutic benefits and broadening its application in combating emerging viral threats. In doing so, we fill a critical gap in literature, offering a comprehensive overview that informs future research and clinical strategies.

Drug delivery systems of remdesivir

RDV exhibits several physicochemical properties that influence its formulation and delivery. It has a molecular weight of approximately 602.6 g/mol and exhibits poor aqueous solubility that varies depending on pH, with higher solubility in acidic conditions [67]. The log P value of RDV is approximately 2.01, suggesting moderate lipid solubility, which can impact its absorption and distribution [67]. According to the biopharmaceutics classification system (BCS), RDV is considered class II [68]. RDV has a pKa of 10.93 (strongest acid) and −2.22 (strongest base), showing 99.85% protonation at physiological pH in molecular docking simulation [32, 69]. Stability studies have shown that RDV solution for infusion is stable for only 24 h at room temperature or 48 h in the refrigerator [67]. These physicochemical characteristics underscore the need for innovative drug delivery systems to enhance RDV’s therapeutic profile, addressing issues of solubility, bioavailability, and stability, thereby supporting its efficacy in treating viral infections. Despite its potential benefits, the World Health Organization (WHO) has cautioned against RDV use due to insufficient clinical data supporting its therapeutic efficacy [70].

This highlights the ongoing need for addressing the limitations of RDV in clinical applications to fully harness its potential as an antiviral agent against respiratory viral infections (Fig. 2). To overcome the above mentioned hurdles and optimize RDV delivery, various drug delivery systems have been investigated. This section explores the strategies and formulations implemented to enhance bioavailability, reduce toxicity, and improve lung targeting of RDV for more effective treatment outcomes. Table 3 summarizes the developed RDV formulations and their key features. Nano-sized carriers offer several advantages owing to their large surface area-to-volume ratio that overcome challenges associated with conventional drug formulations. Drug encapsulation within nanoparticles increase solubility for poorly soluble drugs and confers metabolic stability shielding drugs from enzymatic degradation. This is particularly relevant for orally administered RDV, given its susceptibility to extensive first-pass metabolism. This characteristic allows for the potential enhancement of oral bioavailability, making nanoparticles a viable option for oral administration. Lipid-based nanoparticles, for instance, can leverage lymphatic transport to bypasshepatic metabolism, thus maintaining RDV stability during oral delivery.

In addition, nanoparticles can be tailored to achieve sustained, controlled, or stimuli-responsive drug delivery based on the desired therapeutic profile. This feature is particularly important for RDV that requires targeted and prolonged action within specific physiological compartments for managing complex viral infections such as COVID-19. Moreover, the surface of nanoparticles can be functionalized with a variety of ligands to enable targeted delivery to specific tissues or cells. Additionally, nanoparticle-based inhalations can effectively deposit in the epithelial lining fluid, offering protection from mucociliary clearance as well as alveolar macrophages, and thus facilitate improved interactions with target cells [71]. Additionally, to achieve the potential benefits of the aforementioned RDV combinations, thoughtful drug delivery systems are needed to accommodate the different physicochemical properties of the various drug molecules. Co loading multiple agents within a single nanoparticle system can unify their pharmacokinetics, ensuring their spatial delivery for a synergistically effect [72].

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Table 3 Overview of delivery systems developed for RDV: Summary of research fndings

Taha, M.S., Akram, A. & Abdelbary, G.A. Unlocking the potential of remdesivir: innovative approaches to drug delivery. Drug Deliv. and Transl. Res. (2025). https://doi.org/10.1007/s13346-025-01843-7