Catechol-Modified Polyions in Layer-by-Layer Assembly to Enhance Stability and Sustain Release of Biomolecules: A Bioinspired Approach

Although layer–by–layer (LbL) assembly technique has been successfully used in various areas of nanobiotechnology, some LbL-assembled nanostructures have suffered from a lack of stability when they are exposed to certain changes in aqueous environments. In addition, the interlayer diffusion of polyelectrolytes throughout the film during assembly generally limits the control of film architecture and release characteristics. To overcome these limitations, we have utilized a strategy to conjugate catechol groups, largely present in mussel adhesive proteins, to branched poly(ethyleneimine) (BPEI) and poly(acrylic acid) (PAA). Only a fraction of amine or acid groups are modified with catechol groups, thereby preserving their charged nature for use in LbL assembly, while integrating the beneficial adhesive features of catechol groups into LbL films. The structure, physico–chemical properties, and stability of LbL films composing BPEI and PAA without and with catechol modifications were compared. The incorporation of catechol groups led to a doubling of the average film thickness and linear film growth. Upon exposure to PBS pH 7.4, the catechol-containing LbL films underwent far fewer changes in the degree of ionization and film thickness and exhibited stronger mechanical properties, indicative of their enhanced film stability. Finally, when LbL films with catechol modifications were used as physical barrier layers between radiolabeled 14 C–dextran sulfate ( 14 C–DS) and 3 H–heparin sulfate ( 3 H–HS), we observed two different release rates composed of an abrupt release from the surface of 3 H–HS, together with a sustained release from the underlying 14 C–DS. Overall, these films provide a bioinspired multifunctional platform for the systematic incorporation and assembly of biological therapeutics into controlled release films at physiological conditions for biomedical applications.