Novel particulate antibiotic-loaded platforms as sustained drug delivery systems for bone infection treatment

Bibliographic Details
Main Author: Ferreira, Inês da Fonseca Santos, 1985-1
Publication Date: 2015
Language: eng
Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Download full: http://hdl.handle.net/10451/18378
Summary: Tese de doutoramento, Farmácia (Tecnologia Farmacêutica), Universidade de Lisboa, Faculdade de Farmácia, 2015
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spelling Novel particulate antibiotic-loaded platforms as sustained drug delivery systems for bone infection treatmentTeses de doutoramento - 2015Tese de doutoramento, Farmácia (Tecnologia Farmacêutica), Universidade de Lisboa, Faculdade de Farmácia, 2015The most common infecting microorganisms in bone infections are staphylococci, namely Staphylococcus aureus and Staphylococcus epidermidis. Conventionally, complicated bone infections caused by Gram-positive bacteria are treated with vancomycin. However, emergence of resistant staphylococci to vancomycin led to the increased use of daptomycin, which is bactericidal against resistant staphylococci. However, in severe bone infections, daptomycin efficacy is often limited, due to insufficient drug bioavailability at the infected site and biofilm tolerance; hence novel approaches are needed to enhance daptomycin antibiofilm effect. Over the last decades, polymeric nano-/microparticles have emerged as a worthy strategy to enhance the antibiofilm effect of clinically available antibiotics. In this context, daptomycin was encapsulated into polymeric microparticles composed by poly(methyl methacrylate (PMMA), PMMA-Eudragit RL 100 (EUD) and poly-caprolactone (PCL). Vancomycin-loaded microparticles were also prepared as controls. All particles were obtained by an optimised double emulsion-solvent evaporation method and subsequently freeze-died. The final particles presented a spherical morphology within the micrometre size range, high drug encapsulation and yield of preparation. Additionally, the effect of the microparticles on cell viability of ISO-compliant cells, fibroblasts, and osteoblasts was tested. Although some formulations induced a slight decrease in cell viability, none of them was considered cytotoxic. Bearing in mind the main objective of this work, daptomycin-loaded PMMA-EUD and PCL microparticles presented the highest in vitro drug release, with concentrations above the minimal inhibitory and bactericidal concentration of the tested strains. Nevertheless, the antibacterial activity of all formulations was assessed against planktonic and sessile clinically relevant staphylococci by isothermal microcalorimetry (IMC). Further characterization of microparticles-biofilm interaction, as well as assessment of their effect on biofilm size, structure and metabolic state, was performed by fluorescence in situ hybridization (FISH). Daptomycin-loaded PMMA-EUD and PCL microparticles proved to be the most effective against the tested strains with high antibiofilm activity. Finally, the microencapsulation of daptomycin into polymeric carriers proved to be an advantageous approach, thus making them potential candidates as sustained drug delivery systems for bone infections treatment. In addition, the innovative combination of IMC with FISH was essential in order to gain further insights on the antibiofilm effects of microparticulate systems, as well as on their interaction with sessile bacteria.Fundação para a Ciência e a Tecnologia (FCT), projeto PEst-OE/SAU/UI4013/2011; Fundo Europeu de Desenvolvimento Regional (FEDER)Almeida, António José Leitão das Neves, 1963-Bettencourt, Ana Francisca Campos SimãoTrampuz, AndrejRepositório da Universidade de LisboaFerreira, Inês da Fonseca Santos, 1985-12015-07-06T11:21:30Z201520152015-01-01T00:00:00Zdoctoral thesisinfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10451/18378TID:101375891enginfo:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2025-03-17T13:19:24Zoai:repositorio.ulisboa.pt:10451/18378Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-29T02:40:57.020221Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv Novel particulate antibiotic-loaded platforms as sustained drug delivery systems for bone infection treatment
title Novel particulate antibiotic-loaded platforms as sustained drug delivery systems for bone infection treatment
spellingShingle Novel particulate antibiotic-loaded platforms as sustained drug delivery systems for bone infection treatment
Ferreira, Inês da Fonseca Santos, 1985-1
Teses de doutoramento - 2015
title_short Novel particulate antibiotic-loaded platforms as sustained drug delivery systems for bone infection treatment
title_full Novel particulate antibiotic-loaded platforms as sustained drug delivery systems for bone infection treatment
title_fullStr Novel particulate antibiotic-loaded platforms as sustained drug delivery systems for bone infection treatment
title_full_unstemmed Novel particulate antibiotic-loaded platforms as sustained drug delivery systems for bone infection treatment
title_sort Novel particulate antibiotic-loaded platforms as sustained drug delivery systems for bone infection treatment
author Ferreira, Inês da Fonseca Santos, 1985-1
author_facet Ferreira, Inês da Fonseca Santos, 1985-1
author_role author
dc.contributor.none.fl_str_mv Almeida, António José Leitão das Neves, 1963-
Bettencourt, Ana Francisca Campos Simão
Trampuz, Andrej
Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Ferreira, Inês da Fonseca Santos, 1985-1
dc.subject.por.fl_str_mv Teses de doutoramento - 2015
topic Teses de doutoramento - 2015
description Tese de doutoramento, Farmácia (Tecnologia Farmacêutica), Universidade de Lisboa, Faculdade de Farmácia, 2015
publishDate 2015
dc.date.none.fl_str_mv 2015-07-06T11:21:30Z
2015
2015
2015-01-01T00:00:00Z
dc.type.driver.fl_str_mv doctoral thesis
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/18378
TID:101375891
url http://hdl.handle.net/10451/18378
identifier_str_mv TID:101375891
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron:RCAAP
instname_str FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron_str RCAAP
institution RCAAP
reponame_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
collection Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
repository.name.fl_str_mv Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
repository.mail.fl_str_mv info@rcaap.pt
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