MAD (multiagent delivery) nanolayer: delivering multiple therapeutics from hierarchically assembled surface coatings.

We present hydrolytically degradable polymeric multilayer films that can codeliver multiple therapeutics of differing chemical characteristics (charged biomacromolecules and neutral hydrophobic small molecules) from a surface. This multiagent-delivery (MAD) nanolayer system integrates the hydrolytically degradable poly(beta-amino ester) as a structural component to control the degradation of the multilayers to release active therapeutic macromolecules as well as hydrophobic drugs imbedded within amphiphilic block copolymer micellar carriers within layer-by-layer (LbL) films, which would otherwise be difficult to include within the multilayers. By varying the anionic therapeutic agents (heparin and dextran sulfate) within the multilayer, we examine how different structural components can be used to control the release kinetics of multiple therapeutics from MAD nanolayers. Controlled release profiles and the in vitro efficacy of the MAD nanolayers in suppressing the growth of human smooth muscle cell lines were evaluated. The dual delivery of a charged macromolecular heparin and a small hydrophobic drug, paclitaxel, is found to be synergistic and beneficial toward effective therapeutic activity. Furthermore, we compared the classical dipping method that we employed here with an automated spray-LbL technique. Spray-LbL significantly facilitates film processing time while preserving the characteristic release profiles of the MAD nanolayers. With the highly versatile and tunable nature of LbL assembly, we anticipate that MAD nanolayers can provide a unique platform for delivering multiple therapeutics from macromolecules to small molecules with distinct release profiles for applications in biological and biomedical surface coatings.

Polyelectrolyte multilayers for tunable release of antibiotics.

Polyelectrolyte multilayers incorporating gentamicin were fabricated using layer-by-layer deposition. The multilayers could be precisely tuned with regard to dosage, and release rate under aqueous physiological conditions could be controlled. The films were demonstrated efficacious against Staphylococcus aureus and nontoxic toward murine osteoblasts MC3T3. The films were made in a layer-by-layer process with a heterostructural architecture that represents a general strategy for incorporating charged small molecular species into polyelectrolyte multilayers without the need for any physical or chemical premodification, expanding the range of active species that can be delivered from these films while maintaining the ease of layer-by-layer fabrication process.

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(ß-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.