Enhanced Nasal Deposition and Anti-Coronavirus Effect of Favipiravir-Loaded Mucoadhesive Chitosan–Alginate Nanoparticles
Khent Primo Alcantara,
Nonthaneth Nalinratana,
Nopporn Chutiwitoonchai,
Agnes L. Castillo,
Wijit Banlunara,
Opa Vajragupta,
Pornchai Rojsitthisak,
Pranee Rojsitthisak
Affiliations
Khent Primo Alcantara
Center of Excellence in Natural Products for Ageing and Chronic Diseases, Chulalongkorn University, Bangkok 10330, Thailand
Nonthaneth Nalinratana
Center of Excellence in Natural Products for Ageing and Chronic Diseases, Chulalongkorn University, Bangkok 10330, Thailand
Nopporn Chutiwitoonchai
National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency, Pathum Thani 12120, Thailand
Agnes L. Castillo
Faculty of Pharmacy, The Graduate School, Research Center for the Natural and Applied Sciences (RCNAS), University of Santo Tomas, Manila 1008, Philippines
Wijit Banlunara
Department of Pathology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand
Opa Vajragupta
Center of Excellence in Natural Products for Ageing and Chronic Diseases, Chulalongkorn University, Bangkok 10330, Thailand
Pornchai Rojsitthisak
Center of Excellence in Natural Products for Ageing and Chronic Diseases, Chulalongkorn University, Bangkok 10330, Thailand
Pranee Rojsitthisak
Center of Excellence in Natural Products for Ageing and Chronic Diseases, Chulalongkorn University, Bangkok 10330, Thailand
Favipiravir (FVR) is a repurposed antiviral drug for treating mild to moderate cases of the novel coronavirus disease 2019 (COVID-19). However, its poor solubility and permeability limit its clinical efficacy. To overcome its physicochemical and pharmacokinetic limitations, we statistically designed a mucoadhesive chitosan–alginate nanoparticles (MCS-ALG-NPs) as a new carrier for FVR using response surface methodology, which provided suitable characteristics for transmucosal delivery. The use of mucoadhesive polymers for intranasal administration promotes the residence time and contact of FVR in the mucus membrane. The optimized FVR-MCS-ALG-NPs demonstrated superior mucoadhesion, higher permeation and deposition in the nasal mucosa, and a significant increase in the inhibition of viral replication over 35-fold compared with free FVR. The overall results suggest that MCS-ALG-NPs could be used as an effective mucoadhesive carrier to enhance the activity of FVR against COVID-19.
