Langmuir monolayers of N-acyl derivatives of adefovir phosphonate at the air/water interface and molecular self-assembly in water

Adefovir is a commonly used anti-hepatitis B virus nucleoside analog. Four N-acyl derivatives of adefovir phosphonate with different lipid chains were prepared, including N-decanoyl-1-(3-chlorophenyl)-1,3-propanyl phosphonyl adefovir (DCPA), N-lauroyl-1-(3-chlorophenyl)-1,3-propanyl phosphonyl adefovir( LCPA), N-myristoyl-1-(3-chlorophenyl)-1,3-propanyl phosphonyl adefovir (MCPA) and N-stearoyl-1-(3-chlorophenyl)-1,3-propanyl phosphonyl adefovir (SCPA). They formed the Langmuir monolayers at the air/water interface with a little difference of the surface pressure-molecular area isotherms. Self-assembled nanoassemblies of the derivatives were prepared by injecting their methanol solutions into water. The sizes were 148.2, 169.6 and 159 nm for the nanoassemblies of DCPA, LCPA and MCPA, respectively, and the zeta potentials were -22.2, -16.8 and -13.8 mV, respectively. Flocky precipitates appeared in the suspension of the SCPA nanoassemblies due to aggregation of the nanoassemblies and the strong hydrophobic interaction of SCPA. Dissipative particle dynamics was used to simulate molecular self-assembly of the derivatives in water based on the coarse-grained models. The simulation result was consistent with the experimental results. The nanoassemblies of the derivatives would be promising nanomedicines. (C) 2014 Elsevier B.V. All rights reserved.