Nikhil Prasad Fact checked by:Thailand Medical News Team Jul 28, 2024 3 months, 2 weeks, 3 days, 45 minutes ago
Influenza News: Breakthrough in Influenza Treatment: Inhalable Penindolone-Loaded Nanoparticles
In a significant advancement in the fight against influenza A, researchers from the Ocean University of China, Xuzhou Vocational College of Industrial Technology, Pilot National Laboratory for Marine Science and Technology in Qingdao, and Qingdao Institute for Food and Drug Control have developed a novel antiviral treatment. This new approach covered in this
Influenza News report, utilizes inhalable penindolone-loaded nanoparticles (PND-NPs) that have demonstrated superior efficacy compared to the widely used antiviral drug, oseltamivir.
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China develops new antiviral to combat Influenza A infections
Overcoming Hydrophobicity for Enhanced Efficacy
Penindolone (PND) is a promising inhibitor targeting the HA1 and HA2 subunits of the influenza A virus (IAV) hemagglutinin. Despite its potential, PND's clinical utility has been limited by its poor water solubility and inadequate oral bioavailability. The research team has successfully overcome these obstacles by developing PND-loaded nanoparticles through hydrophobic interactions with monomethoxy poly(ethylene glycol)-poly(D, L-lactide) copolymer, achieving efficient PND loading.
Superior Antiviral Activity and Lower Cytotoxicity
In vitro experiments revealed that PND-NPs exhibit significantly lower cytotoxicity and more potent antiviral activity against IAVs than free PND. The nanoparticles showed an impressive improvement in inhibitory concentration (IC50) against different IAV strains, expanding the therapeutic window. For instance, PND-NPs had an IC50 of 2.5 μM against the A/Virginia/ATCC1/2009 strain and 11 μM against the A/Puerto Rico/8/3 (PR/8) strain, compared to 42.9 μM and 73 μM, respectively, for free PND.
Effective in Animal Models
The efficacy of PND-NPs was further demonstrated in a PR/8-infected mice model. Local delivery of PND-NPs via aerosolized inhalation significantly reduced viral load and pro-inflammatory cytokines in the lungs, prolonging the survival time of infected mice. Remarkably, the survival time was twice as long as that observed in the oseltamivir treatment group, underscoring the potential of PND-NPs as a superior treatment option.
Addressing the Global Health Challenge of Influenza A
Influenza A viruses are responsible for approximately one billion infections and half a million deaths annually worldwide. The existing antiviral treatments, including M2 protein inhibitors, neuraminidase inhibitors like oseltamivir, and viral polymerase inhibitors such as baloxavir, face challenges due to the high mutation rate of the virus, leading to drug resistance. Moreover, these treatments often come with side effects, including nervous system damage. Thus, there is an urgent need for antiviral drugs with novel mechanisms of action.
Targeting Hemagglutinin for Dual Action
The infection cycle of IAVs begi
ns with the virus binding to sialic acid residues on the host cell membrane, mediated by the viral spike protein hemagglutinin (HA). HA consists of two subunits, HA1 and HA2, which play crucial roles in viral attachment and membrane fusion. Penindolone (PND) uniquely inhibits HA by binding to both subunits, thereby blocking the virus's ability to attach and fuse with host cells. This dual action, combined with the highly conserved nature of the HA2 domain, results in a lower risk of drug resistance.
Nanotechnology: A Game-Changer for Drug Delivery
The advent of nanotechnology has revolutionized drug delivery, particularly for hydrophobic drugs like PND. Nanocarriers, such as liposomes, exosomes, and polymeric nanoparticles, offer high drug-loading efficiency, improved cellular uptake, and reduced side effects. The research team utilized mPEG-PDLLA copolymer, known for its biodegradability and low toxicity, to create PND-NPs. This approach not only enhanced the solubility and stability of PND but also improved its antiviral efficacy.
Inhalable Delivery: A Targeted Approach
Local pulmonary delivery of drugs offers several advantages over systemic administration, including high bioavailability, low systemic exposure, and reduced side effects. Inhalation therapy is particularly effective for respiratory infections like IAVs, delivering the drug directly to the site of infection. Previous studies have shown the potential of inhalable nanoparticles in treating pulmonary diseases, and this research confirms their efficacy in combating influenza A.
Promising Clinical Application
The inhalable PND-NPs developed by the research team showed uniform distribution in the lungs of infected mice, effectively preventing weight loss and death. Compared to oseltamivir, PND-NPs significantly lowered alveolar viral load and suppressed lung damage and inflammatory cytokines, including TNF-α, IL-1β, and IL-6. These findings suggest that inhalation therapy with PND-NPs is a promising strategy for treating IAV infections.
The study team has already commenced three different randomized clinical trials and hope to get the product to the local market in a short time.
Conclusion: A New Hope in Antiviral Treatment
The development of inhalable PND-NPs marks a significant milestone in antiviral treatment, offering a potent and targeted approach to combat influenza A infections. By overcoming the hydrophobicity and poor bioavailability of PND, the research team has paved the way for its clinical application. The superior efficacy of PND-NPs compared to oseltamivir highlights their potential as a new standard in the treatment of influenza A. As further clinical trials progress, this innovative treatment could provide a much-needed solution to the global health challenge posed by IAVs.
The study findings were published in the peer reviewed Journal of Drug Delivery Science and Technology.
https://www.sciencedirect.com/science/article/abs/pii/S1773224724005707
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