Síntese, caracterização e estudos em solução de terpolímeros antififílicos termo-sensíveis ao pH: uma perspectiva para obtenção de sistemas transportadores de fármacos
Carregando...
Data
2006-02-17
Autores
Blaz Vieira, Neide Aparecida [UNESP]
Título da Revista
ISSN da Revista
Título de Volume
Editor
Universidade Estadual Paulista (Unesp)
Resumo
A presente tese envolveu a síntese e caracterização de duas séries de polímeros anfifílicos inteligentes. A utilização de quatro monômeros foi feita com o objetivo de se conferir aos polímeros sensibilidade à temperatura e ao pH . Na primeira série, ou série 1, foram sintetizados terpolímeros anfifílicos termo-sensíveis a partir dos monômeros Nisopropilacrilamida (NIPAm), monometacrilato de poli(etilenoglicol)metil éter (PEG) e ndodecilmetacrilato (DOMA), cuja termo-sensibilidade foi controlada variando-se a proporção molar dos monômeros. Os polímeros foram caracterizados utilizando-se as técnicas de ressonância magnética nuclear e cromatografia de permeação em gel (GPC). As propriedades das soluções foram estudadas empregando-se espectrofotometria, fluorescência e espalhamento de luz dinâmico. Os polímeros exibiram temperatura de turvação em solução aquosa entre 17 e 52ºC, dependendo da composição. A proporção do monômero hidrofílico (PEG) foi variada com o objetivo de se obter termo-sensibilidade próxima à temperatura do corpo humano (37° C). O aumento da força iônica das soluções pela adição de KCl reduziu a temperatura de turvação pelo efeito salting out. Os polímeros formaram, em solução aquosa, microdomínios hidrofóbicos, cuja CAC variou de 1,2x10-3 a 1x10-2 g dm-3 , com o aumento da proporção molar de PEG de 5 a 35%. Os agregados hidrofóbicos tipo micelar apresentaram um tamanho que variou de 50 a 140 nm, dependendo da proporção dos monômeros, e mostraram capacidade para incorporar moléculas hidrofóbicas, como pireno e doxorubicina. As quantidades máximas incorporadas foram de, respectivamente, 6,1 mg/g polímero e 13,5 mg/g polímero para pireno e doxorubicina. Agregados mais hidrofóbicos incorporaram uma quantidade maior do hidrófobo.
In the present thesis the synthesis and characterization of two series of intelligent polymers were performed aiming to construct potential drug carriers. Four monomers were employed to provide thermo and pH sensitivity to the systems. In the first series terpolymers of N-isopropylacrylamide, dodecyl methacrylate (DOMA) and poly(ethylene glycol)(PEG) methacrylate, were synthesized by random copolymerization, and the composition was controlled to achieve systems having different thermosensitivities. 1HNMR spectra and gel permeation chromatography (GPC) were employed to characterize the different samples obtained. The solution properties were studied by employing spectrophotometry, fluorescence, and dynamic light scattering techniques. The chemical compositions in the final terpolymers are close to those in the feed and the composition was controlled aiming to adjust the thermosensitivity close to that of the human body temperature (370C). The polymers exhibited cloud point temperatures (Tcs) varying from 17 to 52 0C. Micropolarity studies using I1/I3 ratio of the vibronic bands of pyrene show the formation of amphiphilic aggregates capable of incorporating hydrophobic drugs as the polymer concentration is increased. The critical aggregation concentration (CAC) increases from 1.2x10-3 to 1x10-2 g.L-1 with the PEG content varying from 5 to 35 mol%. Anisotropy measurements confirm the results obtained by pyrene fluorescence and show that the aggregates resulting from intermolecular interactions present different organizations. The hydrodynamic diameters (Dh) of the aggregates determined by dynamic light scattering (DLS) vary from 40 to 150 nm depending on the terpolymer composition. The Tcs and Dh values decreased with the ionic strength, and this behavior was attributed to the dehydration of the polymeric micelles. The capacity of solubilization of the aggregates was evaluated by employing pyrene and adryamicin and the obtained results confirm th
In the present thesis the synthesis and characterization of two series of intelligent polymers were performed aiming to construct potential drug carriers. Four monomers were employed to provide thermo and pH sensitivity to the systems. In the first series terpolymers of N-isopropylacrylamide, dodecyl methacrylate (DOMA) and poly(ethylene glycol)(PEG) methacrylate, were synthesized by random copolymerization, and the composition was controlled to achieve systems having different thermosensitivities. 1HNMR spectra and gel permeation chromatography (GPC) were employed to characterize the different samples obtained. The solution properties were studied by employing spectrophotometry, fluorescence, and dynamic light scattering techniques. The chemical compositions in the final terpolymers are close to those in the feed and the composition was controlled aiming to adjust the thermosensitivity close to that of the human body temperature (370C). The polymers exhibited cloud point temperatures (Tcs) varying from 17 to 52 0C. Micropolarity studies using I1/I3 ratio of the vibronic bands of pyrene show the formation of amphiphilic aggregates capable of incorporating hydrophobic drugs as the polymer concentration is increased. The critical aggregation concentration (CAC) increases from 1.2x10-3 to 1x10-2 g.L-1 with the PEG content varying from 5 to 35 mol%. Anisotropy measurements confirm the results obtained by pyrene fluorescence and show that the aggregates resulting from intermolecular interactions present different organizations. The hydrodynamic diameters (Dh) of the aggregates determined by dynamic light scattering (DLS) vary from 40 to 150 nm depending on the terpolymer composition. The Tcs and Dh values decreased with the ionic strength, and this behavior was attributed to the dehydration of the polymeric micelles. The capacity of solubilization of the aggregates was evaluated by employing pyrene and adryamicin and the obtained results confirm th
Descrição
Palavras-chave
Biologia molecular, Polimeros, Biofísica molecular, Polímeros termosensíveis, Transportador de fármacos, Drugs carriers, Polymers
Como citar
BLAZ VIEIRA, Neide Aparecida. Síntese, caracterização e estudos em solução de terpolímeros antififílicos termo-sensíveis ao pH: uma perspectiva para obtenção de sistemas transportadores de fármacos. 2006. 120 f. Tese (doutorado) - Universidade Estadual Paulista, Instituto de Biociências, Letras e Ciências Exatas, 2006.