Park Junghun, Han Hyogu, Ahn Jun Ki
Department of Biologics, Gachon University, Incheon 21936, Republic of Korea.
User Convenience Technology R&D Department, Korea Institute of Industrial Technology (KITECH), Ansan 15588, Republic of Korea.
Pharmaceutics. 2024 Sep 30;16(10):1288. doi: 10.3390/pharmaceutics16101288.
The SARS-CoV-2 pandemic has highlighted niclosamide (NIC) as a promising treatment for COVID-19. However, its clinical application is limited due to its poor water solubility, resulting in low bioavailability. To address this issue, we developed a AuNP-HA-NIC system, which combines gold nanoparticles with hyaluronic acid to enhance drug delivery. Our comprehensive characterization of the system revealed that hyaluronic acid with specific molecular weights, particularly those exposed to electron-beam irradiation between 2 and 20 kGy, produced the most stable nanoparticles for efficient drug loading and delivery. Additionally, the AuNP-HA-NIC system exhibits a significant sensitivity to pH changes, which is a critical feature for targeted drug release. Under acidic conditions mimicking the stomach and small intestine, minimal drug release was observed, indicating the effective prevention of premature drug release in the gastrointestinal tract. Furthermore, the integration of a targeting aptamer established specific binding abilities towards the SARS-CoV-2 spike protein, distinguishing it from other coronaviruses. As research progresses, and with further in vivo testing and optimization, the AuNP-HA-NIC-aptamer system holds great promise as a game-changer in the field of antiviral therapeutics, particularly in the battle against COVID-19.
严重急性呼吸综合征冠状病毒2(SARS-CoV-2)大流行使氯硝柳胺(NIC)成为治疗新型冠状病毒肺炎(COVID-19)的一种有前景的药物。然而,由于其水溶性差,导致生物利用度低,其临床应用受到限制。为了解决这个问题,我们开发了一种金纳米颗粒-透明质酸-氯硝柳胺(AuNP-HA-NIC)系统,该系统将金纳米颗粒与透明质酸结合以增强药物递送。我们对该系统的全面表征表明,具有特定分子量的透明质酸,特别是那些受到2至20千戈瑞电子束辐照的透明质酸,能产生最稳定的纳米颗粒,用于高效的药物负载和递送。此外,AuNP-HA-NIC系统对pH变化表现出显著的敏感性,这是靶向药物释放的一个关键特征。在模拟胃和小肠的酸性条件下,观察到药物释放极少,这表明有效地防止了药物在胃肠道的过早释放。此外,靶向适体的整合建立了对SARS-CoV-2刺突蛋白的特异性结合能力,使其与其他冠状病毒区分开来。随着研究的进展,以及进一步的体内测试和优化,AuNP-HA-NIC-适体系统在抗病毒治疗领域,特别是在对抗COVID-19的战斗中,有望成为一种变革性的药物。