Concentration-dependent assembly of Bovine serum albumin molecules in the doxorubicin loading process: Molecular dynamics simulation

Bovine serum albumin (BSA) is one of the most investigated proteins, exhibiting high potential for drug delivery. The positively charged doxorubicin (DOX) and negatively charged BSA molecules can interact via non-covalent bonds that can trigger the assembly of BSA and DOX molecules to generate new nanoparticles. We conducted molecular dynamics simulations to assess the concentration-dependent assembly behavior of BSA molecules in the presence of protonated DOXs at physiological pH conditions. Results imply that as molecular concentration increases, the induction of the assembly process leads to larger nanoparticle generation. This is accompanied by the surface charge of new particle to change from negative to positive, and the nanoparticles to contain more protein and loaded DOXs. Moreover, the entire process would provide the stability to the system via improved molecular interactions. In addition, we found the number of DOXs acting as hydrogen bond donor as well as acidic amino acids that contributing to the interactions at such conditions at higher concentrations, remarkable. Ultimately, this study proposes increasing the molecular concentration to improve the drug delivery efficiency by using BSA.