Tunable Drug Release from Hydrolytically Degradable Layer-by-Layer Thin Films

Abstract

The development of new thin film fabrication techniques that allow for precise control of degradation and drug release properties could represent an important advance in the fields of drug delivery and biomedicine. Polyelectrolyte layer-by-layer (LBL) thin films can be assembled with nanometer scale control over spatial architecture and morphology, yet very little work has focused on the deconstruction of these ordered thin films for controlled release applications. In this study, hydrolytically degradable LBL thin films are constructed by alternately depositing a degradable poly(beta-amino ester) (polymer 1) and a series of model therapeutic polysaccharides (heparin, low molecular weight heparin, and chondroitin sulfate). These films exhibit pH-dependent, pseudo-first-order degradation and release behavior. The highly versatile and tunable properties of these materials make them exciting candidates for the controlled release of a wide spectrum of therapeutics.

Structure/Property Relationships in Erodible Multilayered Films: Influence of Polycation Structure on Erosion Profiles and the Release of Anionic Polyelectrolytes

“…41,42 Multilayered films fabricated from polymer 1 typically erode over periods of time ranging from 24 to 48 hours at physiological pH, temperature, and ionic strength. [22][23][24][25][26] In the context of controlled release, these assemblies are therefore limited to the sustained release of incorporated material over relatively short time periods. The development of principles that can be used to reduce erosion rates or otherwise delay release for longer periods of time would contribute to the design of these assemblies for a broader range of therapeutic and controlled release applications.…”

Controlled Drug Delivery From Composites of Nanostructured Porous Silicon and Poly( L -Lactide)

“…Controlled drug delivery systems have now been developed to the point where they can facilitate site-specific delivery at precisely controlled rates [4][5][6][7][8][9]. Control over the delivery rate minimizes the toxicity and side effects of the drug being delivered [1,[10][11][12][13][14][15]. In order for a drug delivery system to provide a therapeutic payload with the maximum therapeutic benefit, the release profile of new drug delivery systems typically need to be carefully adapted to the particular application.…”

Layer-by-Layer-Assembled Multilayer Films for Transcutaneous Drug and Vaccine Delivery

“…[15][16][17] In concert with a growing interest in applying multilayers to biomedical applications, erodible multilayers that deconstruct in aqueous conditions via disassembly and/or breakdown of the constituent polymers have begun to be explored as potential controlled release drug delivery films. [18][19][20][21] Drug-loaded degradable multilayers have been explored for the sustained release of small-molecule antibiotics, protein therapeutics, or plasmid DNA. 3,7,18,19,[21][22][23][24] The mild aqueous conditions for encapsulating molecules into multilayer films preserves the bioactivity of fragile biomolecules such as proteins and nucleic acids.…”

“…[18][19][20][21] Drug-loaded degradable multilayers have been explored for the sustained release of small-molecule antibiotics, protein therapeutics, or plasmid DNA. 3,7,18,19,[21][22][23][24] The mild aqueous conditions for encapsulating molecules into multilayer films preserves the bioactivity of fragile biomolecules such as proteins and nucleic acids. 21,22,25 By employing degradable polyelectrolytes as building blocks, the ability to tune the degradation kinetics of multilayer assemblies has been demonstrated and used to control the release kinetics of compounds embedded in these films.…”