Polyelectrolyte multilayers for tunable release of antibiotics and other therapeutics

Abstract

Polyelectrolyte multilayers (PEMs) were fabricated via the layer-by-layer (LbL) deposition process, incorporating hydrolytically degradable poly([beta]-amino esters) to result in biodegradable PEMs that can release active ingredients in a dosage- and rate-tunable fashion. Specifically, PEMs incorporating several types of antibiotics, ranging from aminoglycosides to antimicrobial peptides (AmPs), were fabricated and characterized; these coatings are intended for applications onto biomedical device surfaces for infection control. In vitro efficacy against Staphylococcus aureus and nontoxicity towards preosteoblasts MC3T3 were demonstrated. In vivo evaluations involving a rabbit osteomyelitis model were undertaken as well. Aside from the development of antimicrobial PEMs, additional projects pursued under this thesis, all in the context of PEM-based drug delivery, include [1] demonstration of the sequential release of two species, [2] assessment of the in vitro activity of anticoagulant films, [3] delivery of siRNAs, [4] evaluation of the biocompatibility of poly([beta]- amino esters), [5] incorporation of cyclodextrins for the purpose of small molecule delivery, [6] incorporation of poly(lactic-co-glycolic acid) (PLGA) nanoparticles encapsulating gentamicin, [7] evaluation of film sterilizability via FDA-approved methods, and [8] design and characterization of a multi-drug coating for orthopedic implants for dual antimicrobial and tissue regenerative actions.