Targeted respiratory viral infection therapy using mucoadhesive nanodrug-polymer conjugates: a comprehensive review

The pulmonary route presents a highly effective approach for treating respiratory infections, enabling targeted drug delivery with rapid absorption and minimal systemic toxicity. Inhalation therapy, which bypasses first-pass metabolism, offers localized treatment for conditions such as COVID-19 and influenza, providing faster relief and reducing hospitalizations. Polymeric drug-conjugate nanoparticles, proven effective in lung cancer therapies, hold promise for viral infections by enhancing drug bioavailability and targeting precision while minimizing side effects. This review explores the potential of aerosol-based antiviral drug delivery systems, specifically focusing on the design, conjugation, and application of polymeric nanoparticles using natural and biodegradable polymers. We highlight the role of mucoadhesive properties and polymer-drug conjugation to improve drug retention through electrostatic interactions with respiratory mucin, critical for effective delivery. Challenges such as aerosolization efficiency, inhaler device design, particle size, and site-specific release are discussed, along with strategies to overcome these hurdles. The use of biodegradable, pH-responsive polymers for controlled release and targeted delivery is emphasized, considering the physiological differences between healthy and infected lungs. Future strategies for scalable, self-administered inhalable polymeric nanodrug conjugates are outlined, with the potential to reduce viral loads, limit transmission, and minimize systemic side effects in the treatment of respiratory viral infections.