Novel strategy to produce a drug delivery system for skin regeneration

Detalhes bibliográficos
Autor(a) principal: Gaspar, Diana Patrícia Rodrigues
Data de Publicação: 2012
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.6/1118
Resumo: Skin lesions are traumatic events that lead to the increase of fluid loss, infections, scarring and locally immunocompromised regions. These injuries can be caused by genetic disorders, acute trauma or even surgical interventions. In these situations, a substantial area of skin can be damaged, often without the possibility of being regenerated. Scientists have put a lot of effort in the development of suitable drug delivery systems suitable to release therapeutic molecules that are required for the initials phases of the wound healing process. Cell microencapsulation arises as an alternative approach for sustained in situ cell delivery. This technology is based on the immobilization of cells within a polymeric matrix, surrounded by a semi-permeable membrane, that isolate the encapsulated cells from the host immune system. Nonstanding, the microparticulate matrix still allows the exchange of nutrients, gases, waste and releasing of bioactive molecules, such as extracellular matrix components and growth factors secreted by cells. Nevertheless, the optimization of cell-based therapy demands the development of alternative strategies to improve cell administration. Alginate has been used for cell microencapsulation, due to its simple gelling process, excellent biocompatibility, biodegradability properties and its stability under in vivo conditions. On the other hand, nanoparticulate systems have been widely used in the biomedical field, as drug delivery devices that can improve the efficiency and widening the applications of the microencapsulation systems. Therefore, the present study aimed to develop biodegradable alginate microparticles that were used for human fibroblasts cells and chitosan nanoparticles encapsulation, in order to improve the wound healing process. To do so, two types of microparticles were firstly produced with alginate and a mixture of alginate and collagen. Subsequently, these carriers were characterized according to their size and geometry by scanning electron microscopy. Confocal images were also acquired to confirm cell encapsulation in microparticles. The cytotoxic profile of the carriers was assessed. Cell release from microparticles was observed over time after encapsulation through optical microscopic analysis. In second part of the work, chitosan nanoparticles loaded with a model protein (bovine serum albumin) were produced and were incorporated in microparticles. The encapsulation efficiency of this protein in nanoparticles was determined. Then, both the morphology and size of these nanoparticles were characterized. The results herein obtained showed that the developed microparticles and nanoparticles can be used as systems tailored for sustainable cells and drug release.
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spelling Novel strategy to produce a drug delivery system for skin regenerationUma nova estratégia para produzir um dispositivo para entrega de fármacos que será usado na regeneração da pelePele - Lesões - RegeneraçãoAlginatoEncapsulamento de célulasMicropartículasNanopartículasQuitosanoSkin lesions are traumatic events that lead to the increase of fluid loss, infections, scarring and locally immunocompromised regions. These injuries can be caused by genetic disorders, acute trauma or even surgical interventions. In these situations, a substantial area of skin can be damaged, often without the possibility of being regenerated. Scientists have put a lot of effort in the development of suitable drug delivery systems suitable to release therapeutic molecules that are required for the initials phases of the wound healing process. Cell microencapsulation arises as an alternative approach for sustained in situ cell delivery. This technology is based on the immobilization of cells within a polymeric matrix, surrounded by a semi-permeable membrane, that isolate the encapsulated cells from the host immune system. Nonstanding, the microparticulate matrix still allows the exchange of nutrients, gases, waste and releasing of bioactive molecules, such as extracellular matrix components and growth factors secreted by cells. Nevertheless, the optimization of cell-based therapy demands the development of alternative strategies to improve cell administration. Alginate has been used for cell microencapsulation, due to its simple gelling process, excellent biocompatibility, biodegradability properties and its stability under in vivo conditions. On the other hand, nanoparticulate systems have been widely used in the biomedical field, as drug delivery devices that can improve the efficiency and widening the applications of the microencapsulation systems. Therefore, the present study aimed to develop biodegradable alginate microparticles that were used for human fibroblasts cells and chitosan nanoparticles encapsulation, in order to improve the wound healing process. To do so, two types of microparticles were firstly produced with alginate and a mixture of alginate and collagen. Subsequently, these carriers were characterized according to their size and geometry by scanning electron microscopy. Confocal images were also acquired to confirm cell encapsulation in microparticles. The cytotoxic profile of the carriers was assessed. Cell release from microparticles was observed over time after encapsulation through optical microscopic analysis. In second part of the work, chitosan nanoparticles loaded with a model protein (bovine serum albumin) were produced and were incorporated in microparticles. The encapsulation efficiency of this protein in nanoparticles was determined. Then, both the morphology and size of these nanoparticles were characterized. The results herein obtained showed that the developed microparticles and nanoparticles can be used as systems tailored for sustainable cells and drug release.As lesões na pele são acontecimentos traumáticos que levam ao aumento da perda de fluidos, a infecções, à formação de cicatrizes e ao aparecimento de regiões imunocomprometidas. Estas feridas podem ser causadas por desordens de origem genética, traumas ou mesmo devido a cirurgias. Deste modo, uma área substancial da pele pode ser danificada, muitas vezes sem a possibilidade de regeneração. Os investigadores têm procurado desenvolver novos sistemas de entrega de drogas, de forma a acelerar o processo de cicatrização. O microencapsulamento celular surgiu recentemente como uma nova abordagem, para entrega controlada e de longa duração de agentes terapêuticos produzidos e secretados pelas próprias células, tais como componentes da matriz extracelular e factores de crescimento, os quais são essenciais para a regeneração. Esta tecnologia tem por base a imobilização de células, dentro de uma matriz polimérica rodeada por uma membrana semi-permeável. Assim, as células não são reconhecidas pelo sistema imunitário do hospedeiro e a membrana permite a difusão de nutrientes e gases para o interior da matriz e a saída das moléculas bioactivas secretadas pelas células e dos resíduos resultantes do metabolismo celular. No entanto, a terapia celular necessita ainda de ser optimizada. O alginato é um polímero que tem sido usado para o encapsulamento celular, devido ao seu fácil processo de gelificação, excelente biocompatibilidade, biodegradabilidade e estabilidade in vivo. Por outro lado, os sistemas nanoparticulados têm sido amplamente utilizados em aplicações biomédicas, por exemplo na produção de dispositivos de entrega direcionada de moléculas bioactivas, uma vez que permitem obter um perfil de libertação controlado. O presente trabalho teve como objectivo o desenvolvimento de micropartículas de alginato para encapsular fibroblastos humanos e nanopartículas de quitosano, com o intuito de futuramente serem usadas como agentes promotores da cicatrização de feridas. Inicialmente, foram produzidos dois tipos de micropartículas, um à base de alginato e outro de alginato com colagénio. As micropartículas produzidas foram caracterizadas quanto ao seu tamanho e geometria por microscopia electrónica de varrimento. Posteriormente, foram também adquiridas imagens de confocal para confirmar o encapsulamento de células nas micropartículas. O perfil citotóxico dos transportadores foi caracterizado através de testes de viabilidade celular, os quais confirmaram a biocompatibilidade dos transportadores. O perfil de libertação das células foi observado por análise microscópica ao longo dos dias. Numa segunda parte do trabalho foram produzidas nanopartículas de quitosano com o objetivo de serem incorporadas nas micropartículas como transportadores de factores de crescimento e, assim, favorecer a cicatrização das feridas. A eficiência de encapsulação das nanopartículas foi avaliada através da incorporação de uma proteína modelo, albumina de soro bovino. Posteriormente fez-se a caracterização da morfologia e do tamanho destas nanopartículas. Os estudos efectuados demonstraram que o sistema desenvolvido é adequado para a libertação de células e moléculas bioativas de forma controlada, prolongada e em concentrações fisiológicas.Universidade da Beira InteriorCorreia, Ilídio Joaquim SobreirauBibliorumGaspar, Diana Patrícia Rodrigues2013-03-25T15:37:09Z2012-062012-06-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10400.6/1118enginfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-12-15T09:36:36Zoai:ubibliorum.ubi.pt:10400.6/1118Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T00:43:02.417420Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Novel strategy to produce a drug delivery system for skin regeneration
Uma nova estratégia para produzir um dispositivo para entrega de fármacos que será usado na regeneração da pele
title Novel strategy to produce a drug delivery system for skin regeneration
spellingShingle Novel strategy to produce a drug delivery system for skin regeneration
Gaspar, Diana Patrícia Rodrigues
Pele - Lesões - Regeneração
Alginato
Encapsulamento de células
Micropartículas
Nanopartículas
Quitosano
title_short Novel strategy to produce a drug delivery system for skin regeneration
title_full Novel strategy to produce a drug delivery system for skin regeneration
title_fullStr Novel strategy to produce a drug delivery system for skin regeneration
title_full_unstemmed Novel strategy to produce a drug delivery system for skin regeneration
title_sort Novel strategy to produce a drug delivery system for skin regeneration
author Gaspar, Diana Patrícia Rodrigues
author_facet Gaspar, Diana Patrícia Rodrigues
author_role author
dc.contributor.none.fl_str_mv Correia, Ilídio Joaquim Sobreira
uBibliorum
dc.contributor.author.fl_str_mv Gaspar, Diana Patrícia Rodrigues
dc.subject.por.fl_str_mv Pele - Lesões - Regeneração
Alginato
Encapsulamento de células
Micropartículas
Nanopartículas
Quitosano
topic Pele - Lesões - Regeneração
Alginato
Encapsulamento de células
Micropartículas
Nanopartículas
Quitosano
description Skin lesions are traumatic events that lead to the increase of fluid loss, infections, scarring and locally immunocompromised regions. These injuries can be caused by genetic disorders, acute trauma or even surgical interventions. In these situations, a substantial area of skin can be damaged, often without the possibility of being regenerated. Scientists have put a lot of effort in the development of suitable drug delivery systems suitable to release therapeutic molecules that are required for the initials phases of the wound healing process. Cell microencapsulation arises as an alternative approach for sustained in situ cell delivery. This technology is based on the immobilization of cells within a polymeric matrix, surrounded by a semi-permeable membrane, that isolate the encapsulated cells from the host immune system. Nonstanding, the microparticulate matrix still allows the exchange of nutrients, gases, waste and releasing of bioactive molecules, such as extracellular matrix components and growth factors secreted by cells. Nevertheless, the optimization of cell-based therapy demands the development of alternative strategies to improve cell administration. Alginate has been used for cell microencapsulation, due to its simple gelling process, excellent biocompatibility, biodegradability properties and its stability under in vivo conditions. On the other hand, nanoparticulate systems have been widely used in the biomedical field, as drug delivery devices that can improve the efficiency and widening the applications of the microencapsulation systems. Therefore, the present study aimed to develop biodegradable alginate microparticles that were used for human fibroblasts cells and chitosan nanoparticles encapsulation, in order to improve the wound healing process. To do so, two types of microparticles were firstly produced with alginate and a mixture of alginate and collagen. Subsequently, these carriers were characterized according to their size and geometry by scanning electron microscopy. Confocal images were also acquired to confirm cell encapsulation in microparticles. The cytotoxic profile of the carriers was assessed. Cell release from microparticles was observed over time after encapsulation through optical microscopic analysis. In second part of the work, chitosan nanoparticles loaded with a model protein (bovine serum albumin) were produced and were incorporated in microparticles. The encapsulation efficiency of this protein in nanoparticles was determined. Then, both the morphology and size of these nanoparticles were characterized. The results herein obtained showed that the developed microparticles and nanoparticles can be used as systems tailored for sustainable cells and drug release.
publishDate 2012
dc.date.none.fl_str_mv 2012-06
2012-06-01T00:00:00Z
2013-03-25T15:37:09Z
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dc.language.iso.fl_str_mv eng
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dc.publisher.none.fl_str_mv Universidade da Beira Interior
publisher.none.fl_str_mv Universidade da Beira Interior
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