A combinatorial study of experimental analysis and mathematical modeling: How do chitosan nanoparticles deliver therapeutics into cells?

Chitosan nanosystems have been widely explored to deliver therapeutic into cells. The cationic nature of the polymer facilitates its entry into the cell via the negatively charged lipid bilayer. Though the interaction is feasible for successful payload delivery, very little is known about the mechanistic aspects and kinetics of interaction of chitosan nanoparticles (Chnps) with the cellular bilayer membrane. Moreover, the precise mechanism of delivery of therapeutic agents by the Chnps is unknown. The polymerbilayer membrane is anticipated to play a crucial role in deciding its ultimate intracellular fate, while delivering its therapeutic payload. Here, we have made an attempt to understand the interaction of Chnps with the cellular membrane for delivering payload, through experimental analysis and predictive mathematical modeling. We observed that the positively charged, mucoadhesive Chnps lack specificity towards a particular cell type, but are rather successful in the intracellular delivery of nucleic acids.