Hydrophobic Effects in the Critical Destabilization and Release Dynamics of Degradable Multilayer Films.
Recent research has highlighted the ability of hydrolytically degradable electrostatic layer-by-layer films to act as versatile drug delivery systems capable of multi-agent release. A key element of these films is the potential to gain precise control of release by evoking a surface-erosion mechanism. Here we sought to determine the extent to which manipulation of chemical structure could be used to control release from hydrolytically degradable layer-by-layer films through modification of the degradable polycation. Toward this goal, films composed of poly(β-amino ester)s, varying only in the choice of diacrylate monomer, and the model biological drug, dextran sulfate, were used to ascertain the role of alkyl chain length, steric hindrance, and hydrophobicity on release dynamics. Above a critical polycation hydrophobicity, as determined using octanol:water coefficients, the film becomes rapidly destabilized and quickly released its contents. These findings indicate that in these unique electrostatic assemblies, hydrolytic susceptibility is dependent not only on hydrophobicity, but a complex balance between hydrophobic composition, charge density, and stability of electrostatic ion pairs. Computational determination of octanol:water coefficients allowed for the reliable prediction of release dynamics. The determination of a correlation between octanol:water coefficient and release duration will enables advanced engineering to produce custom drug delivery systems.
Smith
Renée C
RC
Joint Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139.
Leung
Amy
A
Kim
Byeong-Su
BS
Hammond
Paula T
PT