Tunable staged release of therapeutics from layer-by-layer coatings with clay interlayer barrier

Abstract

In developing new generations of coatings for medical devices and tissue engineering scaffolds, there is a need for thin coatings that provide controlled sequential release of multiple therapeutics while providing a tunable approach to time dependence and the potential for sequential or staged release. Herein, we demonstrate the ability to develop a self-assembled, polymer-based conformal coating, built by using a water-based layer-by-layer (LbL) approach, as a dual-purpose biomimetic implant surface that provides staggered and/or sustained release of an antibiotic followed by active growth factor for orthopedic implant applications. This multilayered coating consists of two parts: a base osteoinductive component containing bone morphogenetic protein-2 (rhBMP-2) beneath an antibacterial component containing gentamicin (GS). For the fabrication of truly stratified composite films with the customized release behavior, we present a new strategy—implementation of laponite clay barriers—that allows for a physical separation of the two components by controlling interlayer diffusion. The clay barriers in a single-component GS system effectively block diffusion-based release, leading to approximately 50% reduction in bolus doses and 10-fold increase in the release timescale. In a dual-therapeutic composite coating, the top GS component itself was found to be an effective physical barrier for the underlying rhBMP-2, leading to an order of magnitude increase in the release timescale compared to the single-component rhBMP-2 system. The introduction of a laponite interlayer barrier further enhanced the temporal separation between release of the two drugs, resulting in a more physiologically appropriate dosing of rhBMP-2. Both therapeutics released from the composite coating retained their efficacy over their established release timeframes. This new platform for multi-drug localized delivery can be easily fabricated, tuned, and translated to a variety of implant applications where control over spatial and temporal release profiles of multiple drugs is desired.

Sustained release of VH and rhBMP-2 from nanoporous magnesium–zinc–silicon xerogels for osteomyelitis treatment and bone repair

“…As a drugdelivery system, the characteristics of nanoporous material such as tunable pore size, large surface area, and high pore volume make it possible to highly efficiently adsorb proteins and/or drug molecules, and provide sustained release from the nanostructured matrices. 26,27 Vh and rhBMP-2 release from n-MZs and MZs xerogels…”

Lab-on-fiber optofluidic platform for in situ monitoring of drug release from therapeutic eluting polyelectrolyte multilayers

“…At predetermined time points, 0.5 mL of sample was collected from the tube and replaced with 0.5 mL of pre-warmed PBS. Details can be found in [8]. …”

“…One such system is therapeutic-eluting polyelectrolyte coatings deposited via layer-by-layer (LbL) assembly for medical implants and tissue scaffolds intended for clinical care of patients, a frontier field of growing attention and impact [7][8][9][10]. Efficacy of the coating requires controlled and sustained release with dose profiles tailored to specific needs.…”

In-situ monitoring of drug release from therapeutic eluting polyelectrolyte multilayers under static and dynamic conditions

“…Even more interesting, through careful design, LbL renders the freedom for the delicate release strategies at planned time scales for different type of therapeutic drugs. For example, Min et al have demonstrated a tunable staged release of antimicrobial drug and bone growth factor from LbL coatings with clay interlayer barrier to achieve a fast release of gentamicin sulfate at the burst release stage for the elimination of the infection of bone implant site, followed by a clay-barrier-prolonged release of a bone-growth factor for the effective enhancement of the bone growth later on [15]. Eluting of drugs depends on many factors such as the physical and chemical properties of both the carriers and drugs in terms of chemical composition, porosity, surface roughness, degradation ability, molecular weight, particle sizes and interactions between drug and the delivering matrix.…”