國家衛生研究院 NHRI:Item 3990099045/15473
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    题名: Pulmonary delivery of remdesivir and dexamethasone encapsulated nanostructured lipid carriers for enhanced inflammatory suppression in lung
    作者: Chen, CW;Chang, CP;Wen, YS;Kuo, CH;Lin, SW;Tsai, JC;Shyong, YJ
    贡献者: Institute of Biotechnology and Pharmaceutical Research
    摘要: The COVID-19 pandemic, originating from the first reported outbreak in China in January 2020, has arguably become the most formidable global health challenge of the 21st century. Characterized by its rapid spread, the virus has profoundly disrupted lives globally, primarily infecting the cells in the respiratory system. Post-infection, it induces intracellular virus replication, causing cell death and lung inflammation. Severe cases may be complicated by lung fibrosis and fatal cytokine storms, emphasizing the need for efficacious treatment strategies that address both viral infection and inflammatory response [1]. The COVID-19 treatment guidelines issued by the US National Institutes of Health in 2022 underscored the importance of both antiviral and immune modulation therapy, with varying recommendations based on the severity of the disease. For patients with mild symptoms, not requiring hospitalization or supplemental oxygen, therapies like Paxlovid and Remdesivir were advocated to expedite recovery [2]. On the contrary, patients with moderate to severe disease necessitating hospitalization were recommended a combined approach of antiviral and immune-modulator therapy. Key agents in these guidelines include Remdesivir, an antiviral drug, and Dexamethasone, an immune-modulator, illustrating the dual importance of combating the virus while controlling the immune response [2]. As end of 2022, Remdesivir remains the only FDA approved therapeutic for COVID-19 treatment. This antiviral medication is a prodrug that readily crosses cell membranes and transforms into its active form, GS-443902. Once inside an infected cell, GS-443902 disrupts the function of viral RNA polymerase, halting the replication of the viral RNA [3, 4]. However, owing to its low oral bioavailability and hydrophobic nature, it must be dissolved using sulfobutylether-beta-cyclodextrin (SBCD) and administered via intravenous (IV) infusion for at least 2 h [2,5]. This extensive administration period significantly hampers the convenience of Remdesivir’s usage. Furthermore, systemic exposure to the drug and SBCD may cause liver and kidney complications, amongst other adverse reactions. Clinical data indicate that the incidence of adverse effects after 5–10 days of treatment ranges from 70 % to 74 %, including severe adverse effects in 21 %–34 % of cases, necessitating premature cessation of treatment [6]. Previous clinical trials have also highlighted that following IV infusion, the concentration of Remdesivir in the lungs maybe insufficient to effectively inhibit viral replication [7]. The rapid metabolism of Remdesivir to GS-441524, a form unable to penetrate cell membranes, during systemic circulation may further limit its therapeutic efficacy in lungs [8].
    日期: 2023-12
    關聯: Journal of Drug Delivery Science and Technology. 2023 Dec;90:Article number 105144.
    Link to: http://dx.doi.org/10.1016/j.jddst.2023.105144
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1773-2247&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:001111134400001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85175793776
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