Multimonth controlled small molecule release from biodegradable thin films

Abstract

Long-term, localized delivery of small molecules from a biodegradable thin film is challenging owing to their low molecular weight and poor charge density. Accomplishing highly extended controlled release can facilitate high therapeutic levels in specific regions of the body while significantly reducing the toxicity to vital organs typically caused by systemic administration and decreasing the need for medical intervention because of its longlasting release. Also important is the ability to achieve high drug loadings in thin film coatings to allow incorporation of significant drug amounts on implant surfaces. Here we report a sustained release formulation for small molecules based on a soluble charged polymer-drug conjugate that is immobilized into nanoscale, conformal, layer-by-layer assembled films applicable to a variety of substrate surfaces. We measured a highly predictable sustained drug release from a polymer thin film coating of 0.5-2.7 μm that continued for more than 14 mo with physiologically relevant drug concentrations, providing an important drug delivery advance. We demonstrated this effect with a potent small molecule nonsteroidal anti-inflammatory drug, diclofenac, because this drug can be used to address chronic pain, osteoarthritis, and a range of other critical medical issues.NSAID | polyelectrolyte multilayers | polymer prodrug

Macrophages with cellular backpacks for targeted drug delivery to the brain

“…1, the backpacks were assembled to contain the enzyme catalase because of its antioxidant properties and potential for treating brain inflammation [24–27]. Although the payload region in this case was customized for catalase assembly, the versatility of LbL assembly enables the loading of a variety of therapeutics ranging from small molecules, to peptides and proteins [16,28–33]. With our catalase-loaded cell backpacks, we characterized their physical properties and biochemical activity.…”

Biosynthetic Polymers as Functional Materials

“…147,148 The Hammond Lab has made considerable progress with these materials for temporary protection and variable-timed release of therapeutic cargos via diffusion, stimuli-response, and/or network degradation. 149−153 For instance, naturally derived LbL films were assembled through electrostatic complexation between anionic poly(β- l -malic acid) and cationic chitosan in aqueous conditions.…”

Heparin-based hydrogels with tunable sulfation & degradation for anti-inflammatory small molecule delivery

“…Due to their low molecular weight, small molecules can rapidly diffuse from the drug delivery system, often resulting in a bolus release of drug. 4,5 Previous methods to fabricate small molecule delivery systems have included layer-by-layer films, microparticles, nanoparticles, and hydrogels. 4,6,7 Multi-month small molecule release has been demonstrated from poly (L-glutamatic acid)-based layer-by-layer films.…”

“…4,5 Previous methods to fabricate small molecule delivery systems have included layer-by-layer films, microparticles, nanoparticles, and hydrogels. 4,6,7 Multi-month small molecule release has been demonstrated from poly (L-glutamatic acid)-based layer-by-layer films. 4 However, though promising, drawbacks to layer-by-layer films include a time-consuming fabrication process and poor small molecule entrapment resulting in exponential drug release kinetics.…”

“…4,6,7 Multi-month small molecule release has been demonstrated from poly (L-glutamatic acid)-based layer-by-layer films. 4 However, though promising, drawbacks to layer-by-layer films include a time-consuming fabrication process and poor small molecule entrapment resulting in exponential drug release kinetics. 8,9 Furthermore, although several methods exist for the incorporation of small molecules into microparticles and nanoparticles, small molecule release is dependent on the amount of surface-associated drug compared to the amount encapsulated within the particles, and it is therefore difficult to achieve linear release in such systems.…”