Development of Targeted Drug Delivery System for the Treatment of SARS-CoV-2 Using Aptamer-Conjugated Gold Nanoparticles

<b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusions:</b> 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.