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Previous issue date: 2014-12-20 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / New drug delivery systems have been used to increase chemotherapy efficacy due
the possible drug resistance of cancer cells. Poly (lactic acid) (PLA) microparticles
are able to reduce toxicity and prolong methotrexate (MTX) release. In addition, the
use of PLA/poloxamer polymer blends can improve drug release due to changes in
the interaction of particles with biological surfaces. The aim of this study was
developing spray dried biodegradable MTX-loaded microparticles and evaluate PLA
interactions with different kinds of Pluronic? (PLUF127 and PLUF68) in order to
modulate drug release. The variables included different drug:polymer (1:10, 1:4.5,
1:3) and polymer:copolymer ratios (25:75, 50:50, 75:25). The precision and accuracy
of spray drying method was confirmed assessing drug loading into particles (75.0-
101.3%). The MTX/PLA microparticles showed spherical shape with an apparently
smooth surface, which was dependent on the PLU ratio used into blends particles.
XRD and thermal analysis demonstrated that the drug was homogeneously
dispersed into polymer matrix, whereas the miscibility among components was
dependent on the used polymer:copolymer ratio. No new drug- polymer bond was
identified by FTIR analysis. The in vitro performance of MTX-loaded PLA
microparticles demonstrated an extended-release profile fitted using Korsmeyer-
Peppas kinetic model. The PLU accelerated drug release rate possible due PLU
leached in the matrix. Nevertheless, drug release studies carried out in cell culture
demonstrated the ability of PLU modulating drug release from blend microparticles.
This effect was confirmed by cytotoxicity observed according to the amount of drug
released as a function of time. Thus, studied PLU was able to improve the
performance of spray dried MTX-loaded PLA microparticles, which can be
successfully used as carries for modulated drug delivery with potential in vivo
application / Novos sistemas de libera??o de f?rmacos v?m sendo utilizados para aumentar a efic?cia de quimioter?picos devido ? poss?vel resist?ncia de c?lulas cancer?genas. As micropart?culas de poli (?cido l?ctico) (PLA) constituem uma alternativa para diminuir a toxicidade e prolongar a libera??o do metotrexato (MTX). Al?m disso, o uso de blendas polim?ricas PLA-polox?meros pode melhorar o perfil de libera??o do f?rmaco devido a mudan?as nas intera??es das part?culas com superf?cies biol?gicas. O objetivo do estudo foi desenvolver micropart?culas biodegrad?veis de MTX produzidas por spray drying e avaliar intera??es PLA-Pluronic? (PLA-PLU) para modular a libera??o do f?rmaco, utilizando diferentes tipos de Pluronic? (PLUF127 e PLUF68). As vari?veis de composi??o inclu?ram raz?es f?rmaco:pol?mero (1:10; 1:4,5; 1:3) e pol?mero:copol?mero (25:75, 50:50, 75:25). A reprodutibilidade e a efic?cia do m?todo de produ??o foram confirmadas pela alta efici?ncia de incorpora??o dos sistemas (75,0-101,3%). As micropart?culas de MTX/PLA apresentaram-se esf?ricas com superf?cie aparentemente lisa. Este formato mostrou-se dependente da raz?o pol?mero:copol?mero nas part?culas contendo blendas. A an?lise t?rmica e a difra??o de raios-X sugerem que h? dispers?o do f?rmaco por toda a matriz, enquanto que a miscibilidade entre os componentes foi dependente da raz?o pol?mero:copol?mero. Nenhuma liga??o qu?mica entre o f?rmaco e o pol?mero foi identificada pela an?lise de FTIR. As micropart?culas de PLA contendo MTX apresentaram perfil de libera??o prolongada com um prevalente modelo cin?tico de Korsmeyer-Peppas. O PLU acelerou a taxa de libera??o do f?rmaco devido a sua poss?vel sa?da da matriz polim?rica. Por outro lado, estudos de libera??o do f?rmaco realizados em cultura de c?lulas demonstraram que o PLU modula a taxa de MTX liberado a partir de micropart?culas contendo blendas. Este efeito foi confirmado pela citotoxicidade dos sistemas estudados, de acordo com a quantidade de f?rmaco liberado em fun??o do tempo. Portanto, o uso de PLU foi capaz de melhorar o perfil de libera??o de micropart?culas de PLA contendo MTX, o qual pode ser utilizado como carreador para modular a libera??o do f?rmaco com potencial aplica??o in vivo
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufrn.br:123456789/13508 |
| Date | 20 December 2014 |
| Creators | Oliveira, Edilene Gadelha de |
| Contributors | CPF:00840406452, http://lattes.cnpq.br/2593509584288129, Pereira, M?rcia Rodrigues, CPF:83115951787, http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4788568T8, Almeida, Y?da Medeiros Bastos de, CPF:39903338449, http://lattes.cnpq.br/3865509948244113, Silva J?nior, Arn?bio Ant?nio |
| Publisher | Universidade Federal do Rio Grande do Norte, Programa de P?s-Gradua??o em Ci?ncias Farmac?uticas, UFRN, BR, Bioan?lises e Medicamentos |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | application/pdf |
| Source | reponame:Repositório Institucional da UFRN, instname:Universidade Federal do Rio Grande do Norte, instacron:UFRN |
| Rights | info:eu-repo/semantics/openAccess |
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