Preparation of Trimethyl Chitosan Nanoparticles for Spike Proteins Delivery

The COVID-19 pandemic has spread around the world, threatening millions of lives. Currently, the vaccine is the most effective therapy against this pandemic. Protein subunit vaccines have been recently attractive because of the easy production and storage, no chance for virus infection, safe and high tolerance. In this research, we prepared a polyion complex (PIC) composed of positively recharged N,N,N-trimethyl chitosan and negatively recharged chondroitin sulfate to deliver spike protein (ProS), an antigen of SAR-COV-2 through oral administration. The result showed that PIC was successfully synthesized with nano-size distributed from 139.7 ± 0.4 to 184.4 ± 0.8 nm by tuning the polymer ratio. Also, the surface charge of PIC was monitored for proper interaction with negatively charged ProS to incorporate ProS in PIC (PIC-ProS). The obtained result indicated that PIC could encapsulate ProS with over 90% efficiency and protect ProS from acidic pH. Furthermore, the ProS release from PIC-ProS was obtained at neutral pH, which is suitable for oral delivery of ProS in the intestine. Finally, PIC-ProS exhibited low cytotoxicity on normal cell lines implying potential of PIC for delivering ProS to develop an effective oral vaccine against COVID-19.