Figure 3.

(A) Schematic representation of a prodrug nanoparticles interacting with cell membrane and cross section of simulated Pro-nifuroxazide nanoparticle structure with segregation of various components of the Pro-nifuroxazide and PEGCE molecules. (B) Conformations of Pro-nifuroxazide as it approaches the membrane. Distances below the images indicate the position of the nifuroxazide group relative to the membrane interface (z=0). Strong interaction of the PAzPC lipid tail with membrane increases the prodrug-membrane binding range and affinity. (C) Potential of mean force curves for individual nifuroxazide (black) or Pro-nifuroxazide (red) molecules inserting into a POPC membrane. The reaction coordinate (the abcissa) is the distance between center of mass of the nifuroxazide moiety and membrane interface. The free energy curves were calculated from −15 to 35 Å, that is, a range between close positioning of the drug moiety to the membrane center at z = −20 Å, and its complete dissociation from the membrane (35 Å).