Tunable Vancomycin Releasing Surfaces for Biomedical Applications

Abstract

Local drug delivery methods allow for the opportunity to supply potent multispectrum antibiotics such as vancomycin hydrochloride to sites of infection, while avoiding systemic toxicity. In this work, layer-by-layer assembly of polymer multilayer films is applied to create vancomycin delivery coatings. By taking advantage of the versatile layer-by-layer spray and dip coating techniques, thin films were generated based on electrostatic and other secondary interactions discovered to exist between the film components. The importance of film interdiffusion during growth in promoting interactions between film components is found to be critical in the direct incorporation of the weakly charged vancomycin drug in these multilayer films. The resulting coatings are engineered with unprecedented drug densities ranging from 17-220 μg mm(-3) (approximately 20 wt%) for films that are micron to submicron scale in thickness, delivering vancomycin over timescales of 4 h to 2.5 days. The released drug is highly effective in inhibiting Staphylococcus aureus growth in vitro. Taking advantage of the difference in release characteristics between dip and spray assembled films, a composite film architecture was engineered to have both a bolus vancomycin release followed by a period of linear sustained drug release. The control over drug densities and release profiles displayed in this work is necessary to address the requirements of varying medical conditions, including those where immediate infection elimination is needed or long term infection prevention is required.

Multilayer, degradable coating as a carrier for the sustained release of antibiotics: Preparation and antimicrobial efficacy in vitro

“…But, even after decades of routine use, its capacity to minimize mesh-related infection is still a matter of debate [6][7][8]. Therefore, one of the new trends in biomedical research is to deliver active compounds directly into the surgical site from the medical device [9,10]. The main objective of these new active prostheses is to not only restore a damaged function, but they also prompt tissue integration [11][12][13], avoid periprosthetic inflammation [14,15] and prevent surface contamination [16][17][18].…”

Multimonth controlled small molecule release from biodegradable thin films

“…A common challenge in any small molecule drug delivery system is the incorporation and subsequent controlled release of poorly charged or low molecular weight species. Our laboratory has investigated a number of LbLbased biodegradable strategies for controlled small molecule release, including direct incorporation of drug into the film (21,22) and physical entrapment in other charged systems (23,24), with a longest sustained release of 3 wk. Changes in the aqueous environment, such as pH or ionic strength, also can facilitate undesirable film deterioration or drug elution that dramatically affects release kinetics (25).…”

Nanocoating for biomolecule delivery using layer-by-layer self-assembly

“…27 Antibiotic-releasing films showed a linear release over 40 h after dip coating, while spray-coated samples released >90% of their cargo within 4 h. Films prepared via spray coating were consistently thinner, smoother, and contained higher drug concentrations than dip-coated films. 28 Thus, spray coating is efficient and can significantly influence the controlled release of its cargo.…”

“…Since vancomycin is a weakly charged molecule, deposition through dip coating resulted in significant interdiffusion. 28 However, one spray cycle occurs over a time scale that is shorter than that of interdiffusion, and thus the drug remains at the surface of the layered structure. This phenomenon yields thick, low-concentration films via dip coating and thin, high-concentration films via spray coating; these films exhibit different release profiles.…”