Síntese de nanopartículas à base do polissacarídeo Anadenanthera macrocarpa (angico) como matriz para incorporação de fármacos

Detalhes bibliográficos
Autor(a) principal: Oliveira, Marilia de Albuquerque
Data de Publicação: 2010
Tipo de documento: Tese
Idioma: por
Título da fonte: Repositório Institucional da Universidade Federal do Ceará (UFC)
Texto Completo: http://www.repositorio.ufc.br/handle/riufc/15672
Resumo: Polysaccharide nanoparticles obtained from Anadenanthera macrocarpa tree exudates (angico gum, AG) and chitosan (CH) were produced by polyelectrolyte complex formation as well as by graft polymerization of acrylic acid onto a AG backbone. The polyelectrolyte complexes (PECs) were obtained by using AG and its carboxymethylated derivatives with degrees of substitution 0.20 and 0.63 as polianions. Reaction parameters investigated were polymer concentration, molar mass, order of solution addition, charge ratio (n+/n-) and AG degree of substitution of carboxymethylated samples. Data revealed that nanoparticles formed by adding AG to CH (AGCH) are in the range of 17.4 to 41.9 nm. Increasing polyelectrolyte concentration led to a decrease in particle size. Larger sizes were observed for charge ratios (n+/n-) > 1. Regarding the molar mass effect, the higher the chitosan molar mass, the larger are the particle sizes. Atomic Force Spectroscopy revealed that for samples with charge ratio n+/n- = 1, particle sizes were 10 and 14 nm, for high (CHa) and low (CHb) chitosan molar mass, respectively. These figures are lower than those analyzed by light scattering measurements (25.1 and 28.2 nm respectively for AGCHa at n+/n- = 1). Nanoparticles prepared using carboxymethylated AG (CMA) have their sizes strongly dependent on charge ratio; for those samples obtained from CMA with degree of substitution (DS) 0.20 and CHa, size distribution is similar to that of AGCHa samples. For samples synthesized with 0.63 DS, size distribution is dependent on charge ratio: for n+/n-< 0.8 similar distribution is observed as those of AGCHa and CMCHa; for n+/n- > 0.8 larger particles (140 - 636 nm) are produced. CMACHa with 0.63 DS, n+/n- = 4, was used as a matrix for chloroquine encapsulation resulting in a efficiency of encapsulation of 43 %. In vitro release was investigated at pH 5.8 and 7.4, a slower release profile being observed at pH 5.8, whereby only 20 % of drug was released in 22 days. Faster release was observed at pH 7.4, where 84 % of drug was released in 6 h, completion being achieved only after 10 days. Data obtained seem to point out that this system can be used for oral drug administration. AG nanoparticles were also produced by acrylic acid radical polymerization on AG backbone, using cerium ammonium nitrate (CAN) as initiator and methylene bisacrylamide as crosslinking agent. It was investigated the effects of glycosidic unit/acrylic acid (GU/AA) and AA/CAN molar ratios on particle size. AG/AA nanoparticles were found to have sizes in the range 6.4 – 19.4 nm, according to GU/AA ratio and an average reaction yield of 56.6 %. Decreasing initiator concentration resulted in low particle size and high polidispersity. By inserting AA onto AG backbone, smaller particle size was obtained than homopolymer one (417 nm). No pH response was found for AG/AA nanoparticles. Bovine serum albumin (BSA) was doped in AG/AA nanoparticles, with an encapsulation efficiency of 50 % resulting in a low release profile, where 69 % of BSA being released in 30 days.
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spelling Síntese de nanopartículas à base do polissacarídeo Anadenanthera macrocarpa (angico) como matriz para incorporação de fármacosSynthesis of nanoparticles the base of polysaccharide Anadenathera macrocarpa (Angico) how to matrix merger of drugsPolissacarideosNanopartículasGomasPolysaccharide nanoparticles obtained from Anadenanthera macrocarpa tree exudates (angico gum, AG) and chitosan (CH) were produced by polyelectrolyte complex formation as well as by graft polymerization of acrylic acid onto a AG backbone. The polyelectrolyte complexes (PECs) were obtained by using AG and its carboxymethylated derivatives with degrees of substitution 0.20 and 0.63 as polianions. Reaction parameters investigated were polymer concentration, molar mass, order of solution addition, charge ratio (n+/n-) and AG degree of substitution of carboxymethylated samples. Data revealed that nanoparticles formed by adding AG to CH (AGCH) are in the range of 17.4 to 41.9 nm. Increasing polyelectrolyte concentration led to a decrease in particle size. Larger sizes were observed for charge ratios (n+/n-) > 1. Regarding the molar mass effect, the higher the chitosan molar mass, the larger are the particle sizes. Atomic Force Spectroscopy revealed that for samples with charge ratio n+/n- = 1, particle sizes were 10 and 14 nm, for high (CHa) and low (CHb) chitosan molar mass, respectively. These figures are lower than those analyzed by light scattering measurements (25.1 and 28.2 nm respectively for AGCHa at n+/n- = 1). Nanoparticles prepared using carboxymethylated AG (CMA) have their sizes strongly dependent on charge ratio; for those samples obtained from CMA with degree of substitution (DS) 0.20 and CHa, size distribution is similar to that of AGCHa samples. For samples synthesized with 0.63 DS, size distribution is dependent on charge ratio: for n+/n-< 0.8 similar distribution is observed as those of AGCHa and CMCHa; for n+/n- > 0.8 larger particles (140 - 636 nm) are produced. CMACHa with 0.63 DS, n+/n- = 4, was used as a matrix for chloroquine encapsulation resulting in a efficiency of encapsulation of 43 %. In vitro release was investigated at pH 5.8 and 7.4, a slower release profile being observed at pH 5.8, whereby only 20 % of drug was released in 22 days. Faster release was observed at pH 7.4, where 84 % of drug was released in 6 h, completion being achieved only after 10 days. Data obtained seem to point out that this system can be used for oral drug administration. AG nanoparticles were also produced by acrylic acid radical polymerization on AG backbone, using cerium ammonium nitrate (CAN) as initiator and methylene bisacrylamide as crosslinking agent. It was investigated the effects of glycosidic unit/acrylic acid (GU/AA) and AA/CAN molar ratios on particle size. AG/AA nanoparticles were found to have sizes in the range 6.4 – 19.4 nm, according to GU/AA ratio and an average reaction yield of 56.6 %. Decreasing initiator concentration resulted in low particle size and high polidispersity. By inserting AA onto AG backbone, smaller particle size was obtained than homopolymer one (417 nm). No pH response was found for AG/AA nanoparticles. Bovine serum albumin (BSA) was doped in AG/AA nanoparticles, with an encapsulation efficiency of 50 % resulting in a low release profile, where 69 % of BSA being released in 30 days.Nanopartículas do polissacarídeo extraído de exsudatos de árvores da Anadenanthera macrocarpa (goma do angico, GA) foram produzidas utilizando como rotas de sínteses a complexação polieletrolítica (CEP) com quitosana (QT) e a copolimerização por enxertia de ácido acrílico (AA). Na rota de complexação polieletrolítica a goma do angico (GA) e seus derivados carboximetilados (CMA) com grau de substituição (GS) de 0,20 e 0,63 foram utilizados como poliânions. Foram investigados alguns parâmetros que influenciam o tamanho da nanopartícula tais como: concentração dos polissacarídeos, ordem de adição das soluções polieletrolíticas, massa molar da quitosana, razão de carga dos polieletrólitos e grau de substituição da goma do angico carboximetilada. Nanopartículas formadas pela adição de GA a quitosana de alta massa molar (QTa) (GAQTA) possuem valores de tamanho variando de 17,4 a 41,9 nm. O aumento da concentração dos polieletrólitos ocasionou uma diminuição nos tamanhos de partículas. Maiores valores de tamanho foram observados para nanopartículas com razão molar de cargas (n+/n-) > 1. Quanto maior a massa molar da quitosana maior o tamanho das nanopartículas. A variação do tamanho com ordem de adição dos polieletrólitos depende de outros fatores como razão molar de cargas e massa molar da quitosana. A análise por microscopia de força atômica das nanopartículas de GAQTa e GAQTb na razão de carga n+/n- = 1 apresentam partículas ovaladas com diâmetros de 10 a 14 nm respectivamente. Estes valores são inferiores ao obtidos por espalhamento de luz (25,1 e 28,2 nm respectivamente para GAQTa e GAQTb na razão de carga n+/n- = 1). O aumento da densidade de carga pela reação de carboximetilação afeta significantemente o tamanho das partículas. Nanopartícula formadas com CMA GS 0,20 e quitosana de alta massa molar (QTA) apresenta valores similares ao observado para nanopartículas de GAQTa (14 a 30 nm). Quando o GS é aumentado para 0,63 as nanopartículas exibem comportamento diferente dependendo da razão de carga (n+/n-) na qual a nanopartículas foi sintetizada. Para valores de n+/n- < 0,8 os tamanhos de partículas são similares aos observados para GAQTa e CMA0,20QTa, entretanto para n+/n- > 0,8 partículas maiores são produzidas (~ 140 a 636 nm). O estudo de incorporação e ensaio in vitro de liberação de cloroquina foi realizado utilizando como matriz nanopartículas de CMA0,63QTa na razão n+/n- igual a 4 (431 nm) devido a esta apresentar maior eficiência de encapsulamento do fármaco. A nanopartícula incorporou 43 % de cloroquina. Em pH 5,8 a liberação de cloroquina foi lenta, liberando apenas 20 % em 22 dias. Em pH 7,4 foi observado que a liberação é mais rápida do que em pH 5,8 tendo liberado 84 % em 6 h, contudo a liberação só atinge o equilíbrio em 10 dias. Analisando o tamanho de partícula e o comportamento da liberação, observa-se que este sistema é promissor para administração via oral deste fármaco. A segunda rota de síntese foi via copolimerização radicalar por enxertia de ácido acrílico. A reação foi realizada utilizando nitrato de amônio cérico (CAN) como iniciador e bis-acrilamida (MBA) como agente reticulante. Foram avaliados os efeitos da razão molar de unidade glicosídica/ácido acrílico (UG/AA) e AA/CAN no tamanho de partícula. As nanopartículas de goma do angico e ácido acrílico tiveram tamanhos variando de 6,4 a 19,4 nm dependendo da razão UG/AA e um rendimento médio de 56,6 %.Diminuindo a quantidade de iniciador observa-se que o diâmetro diminui, entretanto que a polidispersividade aumenta. Nanopartículas só com poli(ácido acrílico) apresentam tamanho superior aos valores observados em presença de goma do angico (417 nm). Apesar da presença de ácido acrílico as nanopartículas de GA/AA o tamanho da nanopartícula não é sensível ao pH do meio. A incorporação de BSA em nanopartículas de GA/AA foi de 50 % sendo a liberação da proteína bem lenta, tendo liberado apenas 69 % da BSA em 30 dias.Paula, Regina Célia Monteiro deOliveira, Marilia de Albuquerque2016-03-22T15:33:57Z2016-03-22T15:33:57Z2010info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfOLIVEIRA, M. A. Síntese de nanopartículas à base do polissacarídeo Anadenanthera macrocarpa (angico) como matriz para incorporação de fármacos. 2010. 127 f. Tese (Doutorado em Química) - Centro de Ciências, Universidade Federal do Ceará, Fortaleza, 2010.http://www.repositorio.ufc.br/handle/riufc/15672porreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccess2020-06-25T12:59:14Zoai:repositorio.ufc.br:riufc/15672Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2020-06-25T12:59:14Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.none.fl_str_mv Síntese de nanopartículas à base do polissacarídeo Anadenanthera macrocarpa (angico) como matriz para incorporação de fármacos
Synthesis of nanoparticles the base of polysaccharide Anadenathera macrocarpa (Angico) how to matrix merger of drugs
title Síntese de nanopartículas à base do polissacarídeo Anadenanthera macrocarpa (angico) como matriz para incorporação de fármacos
spellingShingle Síntese de nanopartículas à base do polissacarídeo Anadenanthera macrocarpa (angico) como matriz para incorporação de fármacos
Oliveira, Marilia de Albuquerque
Polissacarideos
Nanopartículas
Gomas
title_short Síntese de nanopartículas à base do polissacarídeo Anadenanthera macrocarpa (angico) como matriz para incorporação de fármacos
title_full Síntese de nanopartículas à base do polissacarídeo Anadenanthera macrocarpa (angico) como matriz para incorporação de fármacos
title_fullStr Síntese de nanopartículas à base do polissacarídeo Anadenanthera macrocarpa (angico) como matriz para incorporação de fármacos
title_full_unstemmed Síntese de nanopartículas à base do polissacarídeo Anadenanthera macrocarpa (angico) como matriz para incorporação de fármacos
title_sort Síntese de nanopartículas à base do polissacarídeo Anadenanthera macrocarpa (angico) como matriz para incorporação de fármacos
author Oliveira, Marilia de Albuquerque
author_facet Oliveira, Marilia de Albuquerque
author_role author
dc.contributor.none.fl_str_mv Paula, Regina Célia Monteiro de
dc.contributor.author.fl_str_mv Oliveira, Marilia de Albuquerque
dc.subject.por.fl_str_mv Polissacarideos
Nanopartículas
Gomas
topic Polissacarideos
Nanopartículas
Gomas
description Polysaccharide nanoparticles obtained from Anadenanthera macrocarpa tree exudates (angico gum, AG) and chitosan (CH) were produced by polyelectrolyte complex formation as well as by graft polymerization of acrylic acid onto a AG backbone. The polyelectrolyte complexes (PECs) were obtained by using AG and its carboxymethylated derivatives with degrees of substitution 0.20 and 0.63 as polianions. Reaction parameters investigated were polymer concentration, molar mass, order of solution addition, charge ratio (n+/n-) and AG degree of substitution of carboxymethylated samples. Data revealed that nanoparticles formed by adding AG to CH (AGCH) are in the range of 17.4 to 41.9 nm. Increasing polyelectrolyte concentration led to a decrease in particle size. Larger sizes were observed for charge ratios (n+/n-) > 1. Regarding the molar mass effect, the higher the chitosan molar mass, the larger are the particle sizes. Atomic Force Spectroscopy revealed that for samples with charge ratio n+/n- = 1, particle sizes were 10 and 14 nm, for high (CHa) and low (CHb) chitosan molar mass, respectively. These figures are lower than those analyzed by light scattering measurements (25.1 and 28.2 nm respectively for AGCHa at n+/n- = 1). Nanoparticles prepared using carboxymethylated AG (CMA) have their sizes strongly dependent on charge ratio; for those samples obtained from CMA with degree of substitution (DS) 0.20 and CHa, size distribution is similar to that of AGCHa samples. For samples synthesized with 0.63 DS, size distribution is dependent on charge ratio: for n+/n-< 0.8 similar distribution is observed as those of AGCHa and CMCHa; for n+/n- > 0.8 larger particles (140 - 636 nm) are produced. CMACHa with 0.63 DS, n+/n- = 4, was used as a matrix for chloroquine encapsulation resulting in a efficiency of encapsulation of 43 %. In vitro release was investigated at pH 5.8 and 7.4, a slower release profile being observed at pH 5.8, whereby only 20 % of drug was released in 22 days. Faster release was observed at pH 7.4, where 84 % of drug was released in 6 h, completion being achieved only after 10 days. Data obtained seem to point out that this system can be used for oral drug administration. AG nanoparticles were also produced by acrylic acid radical polymerization on AG backbone, using cerium ammonium nitrate (CAN) as initiator and methylene bisacrylamide as crosslinking agent. It was investigated the effects of glycosidic unit/acrylic acid (GU/AA) and AA/CAN molar ratios on particle size. AG/AA nanoparticles were found to have sizes in the range 6.4 – 19.4 nm, according to GU/AA ratio and an average reaction yield of 56.6 %. Decreasing initiator concentration resulted in low particle size and high polidispersity. By inserting AA onto AG backbone, smaller particle size was obtained than homopolymer one (417 nm). No pH response was found for AG/AA nanoparticles. Bovine serum albumin (BSA) was doped in AG/AA nanoparticles, with an encapsulation efficiency of 50 % resulting in a low release profile, where 69 % of BSA being released in 30 days.
publishDate 2010
dc.date.none.fl_str_mv 2010
2016-03-22T15:33:57Z
2016-03-22T15:33:57Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
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dc.identifier.uri.fl_str_mv OLIVEIRA, M. A. Síntese de nanopartículas à base do polissacarídeo Anadenanthera macrocarpa (angico) como matriz para incorporação de fármacos. 2010. 127 f. Tese (Doutorado em Química) - Centro de Ciências, Universidade Federal do Ceará, Fortaleza, 2010.
http://www.repositorio.ufc.br/handle/riufc/15672
identifier_str_mv OLIVEIRA, M. A. Síntese de nanopartículas à base do polissacarídeo Anadenanthera macrocarpa (angico) como matriz para incorporação de fármacos. 2010. 127 f. Tese (Doutorado em Química) - Centro de Ciências, Universidade Federal do Ceará, Fortaleza, 2010.
url http://www.repositorio.ufc.br/handle/riufc/15672
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