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Polyelectrolyte complexes from chitosan and carrageenan: optimization by response surface methodology and method validation

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Polyelectrolyte complexes (PECs) are important emerging materials in the pharmaceutical industry, especially because they are easily prepared in mild conditions, devoid of organic solvents and other harsh conditions. So far, a large number of scientific articles has been published reporting the possible applications of PECs as drug carriers. Polyelectrolytes own unique features, as they join the properties of polymers and electrolytes. These features turn PECs sensitive to the surrounding environment, such as salt concentration, that can considerably alter their formation and characteristics. Therefore, this work encompassed establishing an experimental design to optimize the formation of PECs from two polyelectrolytes, chitosan (CS) and carrageenan (CRG), in the absence and presence of NaCl in different concentrations. For that, preliminary studies were conducted to determine the solubility of CS and CRG in NaCl solutions, as well as the isoelectric point of PECs. Afterwards, an experimental design was established using response surface methodology to predict the size and zeta potential of the PECs, as well as the yield (measured as turbidity) of the obtained colloid. The design was constructed over a range of CS, CRG and NaCl concentrations that varied from 0 to 2 mM, 0 to 1.67 mM, and 0 to 0.06 M, respectively. Response surfaces and contour diagrams that represent the variations of size and zeta potential with the variation of the concentrations of CS, CRG and NaCl were obtained. Under the tested conditions, nanoparticles ranging in 280 - 700 nm and showing ±49 mV of zeta potential were obtained. The design was later validated and was found to predict with high desirability the size and zeta potential of PECs, but unfortunately failed to predict the yield. As a conclusion, PECs formation from CS and CRG in NaCl solutions can be optimized using the experimental design from this study, which resulted in a model that can predict with high credibility the conditions leading to the formation of particles with specific size and zeta potential.
Os complexos polieletrolíticos (PECs) têm vindo a ganhar uma enorme visibilidade na indústria farmacêutica nos últimos anos. Os PECs destacam-se pela fácil preparação, que dispensa o uso de solventes orgânicos. Existem inúmeros artigos na literatura que reportam a aplicabilidade dos PECs na área de veiculação de fármacos, pois devido às características únicas dos polieletrólitos, que reúnem as propriedades de polímeros e eletrólitos, estes compostos terão elevado potencial nesta área. Estas características tornam os PECs altamente sensíveis às características do meio, como por exemplo a força iónica. Sendo assim, procedeuse neste trabalho à construção de um desenho experimental a fim de otimizar a formação de PECs de quitosano (CS) e carragenina (CRG), na presença e ausência de NaCl de diferentes concentrações. Com esse objetivo, realizaram-se estudos preliminares para determinar a solubilidade do CS e da CRG em soluções de NaCl, bem como o ponto isoelétrico dos PECs. Posteriormente, construiu-se um desenho experimental recorrendo à metodologia de superfície de resposta a fim de prever o tamanho, o potencial zeta, e o rendimento dos PECs, medido através da turbidez do colóide. As concentrações mínimas e máximas dos componentes do desenho são 0 - 2 mM, 0 - 1,67 mM, e 0 - 0,06 M de CS, CRG, e NaCl, respetivamente. Obtiveram-se superfícies de resposta assim como diagramas de contorno a partir do desenho experimental. Estes representam as variações do tamanho e do potencial zeta com as variações dos três parâmetros, concentrações de CS, CRG e NaCl. Nas condições estudadas, obtiveram-se PECs de tamanhos que variam entre 280 e 700 nm e potencial zeta de ±49 mV. Procedeu-se, depois, à validação do desenho. O mesmo comprovou-se válido e capaz de prever o tamanho e o potencial zeta dos PECs com alta desejabilidade. No entanto, não se comprovou válido em fazer previsões do rendimento de preparação do colóide. Concluiu-se que se pode otimizar a formação dos PECs de CS e CRG em soluções de NaCl usando o desenho experimental desenvolvido neste estudo, e que este desenho pode prever as condições que permitem a formação de PECs de tamanho e potencial zeta específicos.

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Carrageenan Chitosan Experimental design Polyelectrolyte complexes Response surface methodology

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