Chloroquine and hydroxychloroquine for combating COVID-19: Investigating efficacy and hypothesizing new formulations using Bio/chemoinformatics tools

Hathout, Rania M.; AbdelHamid, Sherihan G.; Metwally, Abdelkader A.

doi:10.1016/j.imu.2020.100446

Cited by 26 publications

(20 citation statements)

References 61 publications

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“…Chloroquine, an antimalarial drug, has been selected as a model drug for encapsulation into the developed niosomes. Chloroquine has been proposed as a potential therapeutic for coronavirus disease 2019 (COVID-19), due to its ability to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) viral entry, transport, and post-entry events [ 14 , 15 , 16 , 17 ]. Recently, the COVID-19 Treatment Guidelines Panel recommended against the use of chloroquine for the treatment of COVID-19 in hospitalized patients and non-hospitalized patients, following oral administration of the drug [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Intratracheal Administration of Chloroquine-Loaded Niosomes Minimize Systemic Drug Exposure

et al. 2021

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Pulmonary administration provides a useful alternative to oral and invasive routes of administration while enhancing and prolonging the accumulation of drugs into the lungs and reducing systemic drug exposure. In this study, chloroquine, as a model drug, was loaded into niosomes for potential pulmonary administration either via dry powder inhalation or intratracheally. Chloroquine-loaded niosomes have been prepared and extensively characterized. Furthermore, drug-loaded niosomes were lyophilized and their flowing properties were evaluated by measuring the angle of repose, Carr’s index, and Hausner ratio. The developed niosomes demonstrated a nanosized (100–150 nm) spherical morphology and chloroquine entrapment efficiency of ca. 24.5%. The FT-IR results indicated the incorporation of chloroquine into the niosomes, whereas in vitro release studies demonstrated an extended-release profile of the drug-loaded niosomes compared to the free drug. Lyophilized niosomes exhibited poor flowability that was not sufficiently improved after the addition of lactose or when cryoprotectants were exploited throughout the lyophilization process. In vivo, intratracheal administration of chloroquine-loaded niosomes in rats resulted in a drug concentration in the blood that was 10-fold lower than the oral administration of the free drug. Biomarkers of kidney and liver functions (i.e., creatinine, urea, AST, and ALT) following pulmonary administration of the drug-loaded nanoparticles were of similar levels to those of the control untreated animals. Hence, the use of a dry powder inhaler for administration of lyophilized niosomes is not recommended, whereas intratracheal administration might provide a promising strategy for pulmonary administration of niosomal dispersions while minimizing systemic drug exposure and adverse reactions.

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Section: Introductionmentioning

confidence: 99%

Intratracheal Administration of Chloroquine-Loaded Niosomes Minimize Systemic Drug Exposure

et al. 2021

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“…Thus, the high compliance of the lung and oral routes and the existence of enabling technologies for fast translation to the clinic make the oral and pulmonary delivery of anakinra a very attractive approach in COVID-19 therapy. Indeed, inhalation could be a pivotal approach against COVID-19, since the lungs represent the main infection site, and thus a therapeutic target, as even confirmed by in silico predictive tools [ 76 , 77 ]. The well-known and above-mentioned advantages of inhaled drugs, particularly in the form of dry powders, could be of great benefit for drugs like anakinra, justifying the likely higher cost of production compared to the injectable form.…”

Section: Discussionmentioning

confidence: 99%

Tackling Immune Pathogenesis of COVID-19 through Molecular Pharmaceutics

et al. 2021

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An increasing number of clinical studies worldwide are investigating the repurposing of antiviral, immune-modulatory, and anti-inflammatory agents to face the coronavirus disease-19 (COVID-19) pandemic. Nevertheless, few effective therapies exist to prevent or treat COVID-19, which demands increased drug discovery and repurposing efforts. In fact, many currently tested drugs show unknown efficacy and unpredictable drug interactions, such that interventions are needed to guarantee access to effective and safe medicines. Anti-inflammatory therapy has proven to be effective in preventing further injury in COVID-19 patients, but the benefit comes at a cost, as targeting inflammatory pathways can imply an increased risk of infection. Thus, optimization of the risk/benefit ratio is required in the anti-inflammatory strategy against COVID-19, which accounts for drug formulations and delivery towards regionalization and personalization of treatment approaches. In this perspective, we discuss how better knowledge of endogenous immunomodulatory pathways may optimize the clinical use of novel and repurposed drugs against COVID-19 in inpatient, outpatient, and home settings through innovative drug discovery, appropriate drug delivery systems and dedicated molecular pharmaceutics.

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“…Overall, these results are encouraging regarding payload prediction. Also, configuring the most important descriptors may be a mirror image to the possible interaction mechanism responsible for affinity during MD simulations and docking calculations [ 69 , 70 , 71 , 72 , 73 , 74 ].…”

Section: Artificial Intelligence and Machine Learningmentioning

confidence: 99%

Evolution of the Computational Pharmaceutics Approaches in the Modeling and Prediction of Drug Payload in Lipid and Polymeric Nanocarriers

et al. 2021

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This review describes different trials to model and predict drug payload in lipid and polymeric nanocarriers. It traces the evolution of the field from the earliest attempts when numerous solubility and Flory-Huggins models were applied, to the emergence of molecular dynamic simulations and docking studies, until the exciting practically successful era of artificial intelligence and machine learning. Going through matching and poorly matching studies with the wet lab-dry lab results, many key aspects were reviewed and addressed in the form of sequential examples that highlighted both cases.

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Chloroquine and hydroxychloroquine for combating COVID-19: Investigating efficacy and hypothesizing new formulations using Bio/chemoinformatics tools

Cited by 26 publications

References 61 publications

Intratracheal Administration of Chloroquine-Loaded Niosomes Minimize Systemic Drug Exposure

Intratracheal Administration of Chloroquine-Loaded Niosomes Minimize Systemic Drug Exposure

Tackling Immune Pathogenesis of COVID-19 through Molecular Pharmaceutics

Evolution of the Computational Pharmaceutics Approaches in the Modeling and Prediction of Drug Payload in Lipid and Polymeric Nanocarriers

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