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.
Description:
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2008.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student submitted PDF version of thesis.Includes bibliographical references (p. 348-365).
