2026-09-18T21:56:39Zhttps://dspace.mit.edu/server/oai/request

oai:dspace.mit.edu:1721.1/769032022-01-13T07:54:19Zcom_1721.1_7582com_1721.1_7581col_1721.1_131022

Paula T. Hammond. Moskowitz, Joshua Seth Massachusetts Institute of Technology. Dept. of Chemical Engineering. Massachusetts Institute of Technology. Department of Chemical Engineering 2013-02-14T15:15:45Z 2013-02-14T15:15:45Z 2012 2012 http://hdl.handle.net/1721.1/76903 824132546 Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2012. Cataloged from PDF version of thesis. Includes bibliographical references (p. 186-203). Polyelectrolyte multilayered (PEM) coatings were fabricated to incorporate and release the small, hydrophilic antibiotic gentamicin from implant surfaces for infection control. The use of a cationic hydrolytically cleavable poly(p-amino ester) rendered these films biodegradable, yielding both diffusion-based and surface-erosion based release of this therapeutic. The Layer-by- Layer (LbL) assembly platform was used to create conformal, micron scale reservoirs with highly tunable drug release. Film release profiles were engineered through film architecture design and post-processing crosslinking techniques. Delivery of gentamicin was sustained for weeks, which is a significant improvement from previous gentamicin-releasing LbL systems. To gain better insight on the mechanisms of release and aid in rational film design, a theoretical treatment of the physical system was performed. These results include an analytical mathematical model describing the release of drug per surface area of film as a function of time as well as a computational model that simulates the time-dependent concentration profiles in these LbL systems. These erodible, antibiotic coatings were demonstrated to be bactericidal against Staphylococcus aureus, an infectious microorganism that is highly relevant to implant-related infections. Film degradation products were generally nontoxic toward MC3T3-E1 osteoprogenitor cells. A reproducible in vivo rabbit bone infection model was developed to test the PEM coatings against sterile, uncoated placebos; subsequent in vivo experimentation demonstrated the proof-of-principle that an antibiotic-eluting LbL film can efficaciously treat a pre-existing implant-related infection. One further application was studied which combined the release-based mechanism of these erodible films with a permanent, contact-killing LbL film. This combination has the treatment benefit of an initial burst release of antibiotic, prevents biofilm formation, and reduces the probability of developing antibiotic resistance due to the prolonged presence of sublethal concentrations of gentamicin. by Joshua Seth Moskowitz. Ph.D. 203 p. eng Massachusetts Institute of Technology M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 Chemical Engineering. Controlled release of gentamicin from polyelectrolyte multilayers to treat implant-related infection Thesis application/pdf false Publication unknown unknown <Publication xmlns="https://www.openaire.eu/cerif-profile/1.1/" id="896f201c-8763-46a2-85ed-80a16d724f5b"> <Type xmlns="https://www.openaire.eu/cerif-profile/vocab/COAR_Publication_Types">http://purl.org/coar/resource_type/c_1843</Type> <Language>eng</Language> <Title>Controlled release of gentamicin from polyelectrolyte multilayers to treat implant-related infection</Title> <PublishedIn> <Publication> </Publication> </PublishedIn> <PublicationDate>2012</PublicationDate> <Authors> <Author> <DisplayName>Moskowitz, Joshua Seth</DisplayName> <Affiliation> <OrgUnit> </OrgUnit> </Affiliation> </Author> </Authors> <Editors> </Editors> <Publishers> <Publisher> <DisplayName>Massachusetts Institute of Technology</DisplayName> <OrgUnit /> </Publisher> </Publishers> <License>http://dspace.mit.edu/handle/1721.1/7582</License> <Keyword>Chemical Engineering.</Keyword> <Abstract>Polyelectrolyte multilayered (PEM) coatings were fabricated to incorporate and release the small, hydrophilic antibiotic gentamicin from implant surfaces for infection control. The use of a cationic hydrolytically cleavable poly(p-amino ester) rendered these films biodegradable, yielding both diffusion-based and surface-erosion based release of this therapeutic. The Layer-by- Layer (LbL) assembly platform was used to create conformal, micron scale reservoirs with highly tunable drug release. Film release profiles were engineered through film architecture design and post-processing crosslinking techniques. Delivery of gentamicin was sustained for weeks, which is a significant improvement from previous gentamicin-releasing LbL systems. To gain better insight on the mechanisms of release and aid in rational film design, a theoretical treatment of the physical system was performed. These results include an analytical mathematical model describing the release of drug per surface area of film as a function of time as well as a computational model that simulates the time-dependent concentration profiles in these LbL systems. These erodible, antibiotic coatings were demonstrated to be bactericidal against Staphylococcus aureus, an infectious microorganism that is highly relevant to implant-related infections. Film degradation products were generally nontoxic toward MC3T3-E1 osteoprogenitor cells. A reproducible in vivo rabbit bone infection model was developed to test the PEM coatings against sterile, uncoated placebos; subsequent in vivo experimentation demonstrated the proof-of-principle that an antibiotic-eluting LbL film can efficaciously treat a pre-existing implant-related infection. One further application was studied which combined the release-based mechanism of these erodible films with a permanent, contact-killing LbL film. This combination has the treatment benefit of an initial burst release of antibiotic, prevents biofilm formation, and reduces the probability of developing antibiotic resistance due to the prolonged presence of sublethal concentrations of gentamicin.</Abstract> <Access xmlns="http://purl.org/coar/access_right" > </Access> </Publication>