Desenvolvimento de sistemas lipídicos nanoestruturados contendo paclitaxel: estudos de permeação cutânea

Detalhes bibliográficos
Autor(a) principal: Tosta, Fabiana Vaz
Data de Publicação: 2014
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UFG
dARK ID: ark:/38995/0013000004nhp
Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tde/3004
Resumo: Paclitaxel (PTX) is a natural product extracted from the bark of the Pacific Yew and has numerous antitumor actions, including skin cancers. The topical treatment of skin and pre-cancerous lesions cancer is desired, since the systemic treatment has many side effects However, PTX to be incorporated into formulations suitable for it to penetrate the stratum corneum and skin tumors reached. Lipid nanoparticles have potential to increase drug retention in the stratum corneum, thus providing controlled release and great percutaneous absorption. Within this context, the aim of this study was to develop and characterize solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) containing the antineoplastic PTX and evaluate its permeation into the pig ear skin in vertical diffusion cells type "Franz". Quantification of PTX paclitaxel was performed by high performance liquid chromatography. The NLS and CLNs were obtained by the method of dilution of the microemulsion containingcetylpyridinium chloride, glyceryl behenate, triglycerides of caprylic / capric acid, polysorbate 80 and sorbitan trioleate 85. The particles were characterized by medium size, PdI, zeta potential, encapsulation efficiency, drug loading and recovery. Stability studies were carried out for a period of 30 days with storage at 4 °C (± 2 °C). Theskin permeation studies of the PTX nanoparticles were conducted in “Franz” type diffusion cells in pig ear skin. The NLS obtained showed average size of 314.1 ± 10.9 to 335.9 ± 0.9nm. The CLN obtained with more oil in the lipid matrix (CLN100)showed average size 270.6 ± 13.5 nm. The encapsulation efficiency of the systemsobtained was above 90% when 3.75% was added PTX formulations. The stability studies revealed a trend in increasing the size of the particles PdI along the storage period, but these differences are not statistically significant. The CLN100 increased about 3 times the amount of drug in the stratum corneum (SC) as compared to the administration of unencapsulated drug and also increased by 1.5 times the amount of PTX in the SC in relation to the topical application of other lipid particles. Thus, the lipid particles appear to be promising systems for topical application of PTX.
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spelling Taveira, Stephânia Fleuryhttp://lattes.cnpq.br/0382450621383005LIma, Eliana MartinsTaveira, Stephânia FleuryMarreto, Ricardo NevesLopes, Flávio Marqueshttp://lattes.cnpq.br/9825432298411673Tosta, Fabiana Vaz2014-09-03T21:30:23Z2014-09-032014-01-29TOSTA, Fabiana Vaz. Desenvolvimento de sistemas lipídicos nanoestruturados contendo paclitaxel: estudos de permeação cutânea. 2014. 57 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia, 2014.http://repositorio.bc.ufg.br/tede/handle/tde/3004ark:/38995/0013000004nhpPaclitaxel (PTX) is a natural product extracted from the bark of the Pacific Yew and has numerous antitumor actions, including skin cancers. The topical treatment of skin and pre-cancerous lesions cancer is desired, since the systemic treatment has many side effects However, PTX to be incorporated into formulations suitable for it to penetrate the stratum corneum and skin tumors reached. Lipid nanoparticles have potential to increase drug retention in the stratum corneum, thus providing controlled release and great percutaneous absorption. Within this context, the aim of this study was to develop and characterize solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) containing the antineoplastic PTX and evaluate its permeation into the pig ear skin in vertical diffusion cells type "Franz". Quantification of PTX paclitaxel was performed by high performance liquid chromatography. The NLS and CLNs were obtained by the method of dilution of the microemulsion containingcetylpyridinium chloride, glyceryl behenate, triglycerides of caprylic / capric acid, polysorbate 80 and sorbitan trioleate 85. The particles were characterized by medium size, PdI, zeta potential, encapsulation efficiency, drug loading and recovery. Stability studies were carried out for a period of 30 days with storage at 4 °C (± 2 °C). Theskin permeation studies of the PTX nanoparticles were conducted in “Franz” type diffusion cells in pig ear skin. The NLS obtained showed average size of 314.1 ± 10.9 to 335.9 ± 0.9nm. The CLN obtained with more oil in the lipid matrix (CLN100)showed average size 270.6 ± 13.5 nm. The encapsulation efficiency of the systemsobtained was above 90% when 3.75% was added PTX formulations. The stability studies revealed a trend in increasing the size of the particles PdI along the storage period, but these differences are not statistically significant. The CLN100 increased about 3 times the amount of drug in the stratum corneum (SC) as compared to the administration of unencapsulated drug and also increased by 1.5 times the amount of PTX in the SC in relation to the topical application of other lipid particles. Thus, the lipid particles appear to be promising systems for topical application of PTX.O paclitaxel (PTX) é um produto natural extraído da casca do Teixo do Pacífico e possui númeras ações antitumorais, inclusive em neoplasias cutâneas. O tratamento tópico do câncer de pele e de lesões pré-cancerígenas é almejado, visto que o tratamento sistêmico possui diversos efeitos colaterais. Entretanto, o PTX precisa ser incorporado em formulações adequadas para que o mesmo penetre no estrato córneo e atinja os tumores cutâneos. As nanopartículas lipídicas apresentampotencial para aumentar a retenção de fármacos no estrato córneo, proporcionandouma liberação controlada e um aumento na absorção percutânea. Dentro destecontexto, o objetivo deste trabalho foi desenvolver e caracterizar nanopartículaslipídicas sólidas (NLS) e carreadores lipídicos nanoestruturados (CLN) contendo o antineoplásico PTX e avaliar sua permeação cutânea em pele de orelha de suíno em células de difusão vertical tipo “Franz”. A quantificação do paclitaxel PTX foi realizada por cromatografia líquida de alta eficiência. As NLS e CLN foram obtidas pelo método de diluição da microemulsão contendo cloreto de cetilpiridínio, behenato de glicerila, triglicerídeos do ácido cáprico/ caprílico, polissorbato 80 e trioleato de sorbitano 85. As partículas foram caracterizadas quanto ao tamanho médio, PdI, potencial zeta, eficiência de encapsulação, carga de fármaco e recuperação. Os estudos de estabilidade foram realizados por um período de 30 dias com armazenamento a 4°C (± 2°C). Os estudos de permeação cutânea do PTX nas nanopartículas foram realizados em células de difusão tipo “Franz” em pele de orelha de suíno. As NLS obtidas apresentaram tamanho médio entre 314,1 ± 10,9 a 335,9 ± 0,9nm. Os CLN obtidos com mais óleo na matriz lipídica (CLN100), apresentaram tamanho médio 270,6 ± 13,5nm. A eficiência de encapsulação dos sistemas obtidos foi superior a 90% quando 3,75% de PTX foi adicionado as formulações. Nos estudos de estabilidade observou-se uma tendência no aumento do tamanho e PdI das partículas ao longo do período de armazenamento, porém estas diferenças não são estatisticamente significativas. Os CLN100 aumentaram aproximadamente 3 vezes a quantidade de fármaco no estrato córneo (EC) quando comparados com a administração do fármaco não encapsulado e, ainda ,aumentaram 1,5 vezes a quantidade de PTX no EC em relação à aplicação tópica das demais partículas lipídicas. Desta forma, as partículas lipídicas parecem ser sistemas promissores para aplicação tópica do PTX.Submitted by Marlene Santos (marlene.bc.ufg@gmail.com) on 2014-09-03T21:30:23Z No. of bitstreams: 2 DISSET Correção FINAL 03-07-14 FOLHA PDF.pdf: 1467526 bytes, checksum: 196b53fbd9a59de359b14f8fd82c2ee5 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5)Made available in DSpace on 2014-09-03T21:30:23Z (GMT). No. of bitstreams: 2 DISSET Correção FINAL 03-07-14 FOLHA PDF.pdf: 1467526 bytes, checksum: 196b53fbd9a59de359b14f8fd82c2ee5 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2014-01-29Fundação de Amparo à Pesquisa do Estado de Goiás - FAPEGapplication/pdfhttp://repositorio.bc.ufg.br/tede/retrieve/7081/DISSET%20Corre%c3%a7%c3%a3o%20FINAL%2003-07-14%20FOLHA%20PDF.pdf.jpgporUniversidade Federal de GoiásPrograma de Pós-graduação em Ciências Farmacêuticas (FF)UFGBrasilFaculdade Farmácia - FF (RG)ALEXANDER, A.; DWIVEDI, S.; AJAZUDDIN; GIRI, T. K.; SARAF, S.; SARAF, S.; TRIPATHI, D. k. Approaches for breaking the barriers of drug permeation through transdermal drug delivery. Journal of Controlled Release, v. 164 , n.1-2, p. 26-40, 2012. ALVAREZ-ROMAN, R.; NAIK, A.; KALIA, Y. N.; GUY, R.H.; FESSI, H. Skin penetration and distribution of polymeric nanoparticles. Journal of Controlled Release, v. 99, n. 1, p. 53-62, 2004. ASBIL, C. 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Importance of solid lipid nanoparticles (SLN) in variousadministration routes and future perspectives. International Journal of Nanomedicine, v. 2, n. 3, p. 289-300, 2007. WIERNIK, P. H.; SCHWARTZ, E. L.; EINZIG, A.; STRAUMAN, J. J.; LIPTON, R. B.; DUTCHER, J. P. Phase I trial of taxol given as a 24-hour infusion every 21 days: responses observed in metastatic melanoma. Journal of Clinical Oncology, v. 5, n. 8, p. 1232-1239,1987. WISSING, S. A.; KAYSER, O.; MULLER, R. H. Solid lipid nanoparticles for parenteral drug delivery. Advanced Drug Delivery Reviews, v. 56, n. 9, p. 1257-1272, 2004. YANG, X. -Y.; LI, Y. -X.; LI, M.; ZHANG, L.; FENG, L. -X.; ZHANG, N. Hyaluronic acid-coated nanostructured lipid carriers for targeting paclitaxel to cancer. Cancer Letters, v. 334, n. 2, p. 338-445, 2013. YARDLEY, D. A. nab-Paclitaxel mechanisms of action and delivery. Journal of Controlled Release, v. 170, n. 3, p. 365-372, 2013. YUAN, H.; MIAO, J.; DU, Y-Z.; YOU, J.; HU, F-Q.; ZENG, S. Cellular uptake of solidlipid anoparticles and cytotoxicity of encapsulated paclitaxel in A549 cancer cells. International Journal of Pharmaceutics, v. 348, n. 1-2, p. 137-145, 2008. ZHANG, J.; SMITH, E. Percutaneous permeation of betamethasone 17-valerate incorporated in lipid nanoparticles. 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dc.title.por.fl_str_mv Desenvolvimento de sistemas lipídicos nanoestruturados contendo paclitaxel: estudos de permeação cutânea
dc.title.alternative.eng.fl_str_mv Devolopment of placlitaxel- loaded lipid nanoparticles: skin permeation sudies
title Desenvolvimento de sistemas lipídicos nanoestruturados contendo paclitaxel: estudos de permeação cutânea
spellingShingle Desenvolvimento de sistemas lipídicos nanoestruturados contendo paclitaxel: estudos de permeação cutânea
Tosta, Fabiana Vaz
Nanopartículas lipídicas sólidas
Carreadores lipídicos nanoestruturados
Câncer de pele
Paclitaxel
Olid lipid nanoparticles
Nanostructured lipid carriers
Skin cancer
CIENCIAS BIOLOGICAS::FARMACOLOGIA
title_short Desenvolvimento de sistemas lipídicos nanoestruturados contendo paclitaxel: estudos de permeação cutânea
title_full Desenvolvimento de sistemas lipídicos nanoestruturados contendo paclitaxel: estudos de permeação cutânea
title_fullStr Desenvolvimento de sistemas lipídicos nanoestruturados contendo paclitaxel: estudos de permeação cutânea
title_full_unstemmed Desenvolvimento de sistemas lipídicos nanoestruturados contendo paclitaxel: estudos de permeação cutânea
title_sort Desenvolvimento de sistemas lipídicos nanoestruturados contendo paclitaxel: estudos de permeação cutânea
author Tosta, Fabiana Vaz
author_facet Tosta, Fabiana Vaz
author_role author
dc.contributor.advisor1.fl_str_mv Taveira, Stephânia Fleury
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/0382450621383005
dc.contributor.advisor-co1.fl_str_mv LIma, Eliana Martins
dc.contributor.referee1.fl_str_mv Taveira, Stephânia Fleury
dc.contributor.referee2.fl_str_mv Marreto, Ricardo Neves
dc.contributor.referee3.fl_str_mv Lopes, Flávio Marques
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/9825432298411673
dc.contributor.author.fl_str_mv Tosta, Fabiana Vaz
contributor_str_mv Taveira, Stephânia Fleury
LIma, Eliana Martins
Taveira, Stephânia Fleury
Marreto, Ricardo Neves
Lopes, Flávio Marques
dc.subject.por.fl_str_mv Nanopartículas lipídicas sólidas
Carreadores lipídicos nanoestruturados
Câncer de pele
Paclitaxel
topic Nanopartículas lipídicas sólidas
Carreadores lipídicos nanoestruturados
Câncer de pele
Paclitaxel
Olid lipid nanoparticles
Nanostructured lipid carriers
Skin cancer
CIENCIAS BIOLOGICAS::FARMACOLOGIA
dc.subject.eng.fl_str_mv Olid lipid nanoparticles
Nanostructured lipid carriers
Skin cancer
dc.subject.cnpq.fl_str_mv CIENCIAS BIOLOGICAS::FARMACOLOGIA
description Paclitaxel (PTX) is a natural product extracted from the bark of the Pacific Yew and has numerous antitumor actions, including skin cancers. The topical treatment of skin and pre-cancerous lesions cancer is desired, since the systemic treatment has many side effects However, PTX to be incorporated into formulations suitable for it to penetrate the stratum corneum and skin tumors reached. Lipid nanoparticles have potential to increase drug retention in the stratum corneum, thus providing controlled release and great percutaneous absorption. Within this context, the aim of this study was to develop and characterize solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) containing the antineoplastic PTX and evaluate its permeation into the pig ear skin in vertical diffusion cells type "Franz". Quantification of PTX paclitaxel was performed by high performance liquid chromatography. The NLS and CLNs were obtained by the method of dilution of the microemulsion containingcetylpyridinium chloride, glyceryl behenate, triglycerides of caprylic / capric acid, polysorbate 80 and sorbitan trioleate 85. The particles were characterized by medium size, PdI, zeta potential, encapsulation efficiency, drug loading and recovery. Stability studies were carried out for a period of 30 days with storage at 4 °C (± 2 °C). Theskin permeation studies of the PTX nanoparticles were conducted in “Franz” type diffusion cells in pig ear skin. The NLS obtained showed average size of 314.1 ± 10.9 to 335.9 ± 0.9nm. The CLN obtained with more oil in the lipid matrix (CLN100)showed average size 270.6 ± 13.5 nm. The encapsulation efficiency of the systemsobtained was above 90% when 3.75% was added PTX formulations. The stability studies revealed a trend in increasing the size of the particles PdI along the storage period, but these differences are not statistically significant. The CLN100 increased about 3 times the amount of drug in the stratum corneum (SC) as compared to the administration of unencapsulated drug and also increased by 1.5 times the amount of PTX in the SC in relation to the topical application of other lipid particles. Thus, the lipid particles appear to be promising systems for topical application of PTX.
publishDate 2014
dc.date.accessioned.fl_str_mv 2014-09-03T21:30:23Z
dc.date.available.fl_str_mv 2014-09-03
dc.date.issued.fl_str_mv 2014-01-29
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.citation.fl_str_mv TOSTA, Fabiana Vaz. Desenvolvimento de sistemas lipídicos nanoestruturados contendo paclitaxel: estudos de permeação cutânea. 2014. 57 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia, 2014.
dc.identifier.uri.fl_str_mv http://repositorio.bc.ufg.br/tede/handle/tde/3004
dc.identifier.dark.fl_str_mv ark:/38995/0013000004nhp
identifier_str_mv TOSTA, Fabiana Vaz. Desenvolvimento de sistemas lipídicos nanoestruturados contendo paclitaxel: estudos de permeação cutânea. 2014. 57 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia, 2014.
ark:/38995/0013000004nhp
url http://repositorio.bc.ufg.br/tede/handle/tde/3004
dc.language.iso.fl_str_mv por
language por
dc.relation.program.fl_str_mv 824936988196152412
dc.relation.confidence.fl_str_mv 600
600
600
600
dc.relation.department.fl_str_mv 6010281161524209375
dc.relation.cnpq.fl_str_mv 700814650651154363
dc.relation.sponsorship.fl_str_mv -961409807440757778
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