RESUMO
Nanohydrogel particles of polyethylene glycol (PEG), gelatin (GEL), and PEG-GEL mixtures (MIXs) were synthesized with a high electron beam and 60Co gamma-ray radiation. The relatively novel technique of Asymmetrical Flow Field Flow Fractionation (AF4 or AFFFF) coupled to a Multi-Angle Laser Light Scattering (MALLS) detector was mainly used to determine the hydrodynamic diameter (Dh) of the radiation-synthesized PEG, GEL, and PEG-GEL nanohydrogel particles. Our approach to achieving nanohydrogel particles is to enhance the intracrosslinking reactions and decrease the intercrosslinking reactions of the C-centered radicals of the PEG and GEL. The intracrosslinking reactions of these free radicals were enhanced via irradiation at temperatures of 77-80 °C and using a high dose rate and pulsed irradiation. The shorter average distance between the C-centered free radicals on the backbone of the thermally collapsed PEG and GEL chain, due to the destruction of hydrogen bonds, enhances the intracrosslinking reactions. It was observed that increasing the dose and dose rate decreased the Dh. DLS results lined up with AF4 measurements. This study provides researchers with a clean method to produce GEL-PEG hydrogels without the use of toxic reagents. Particle size can be tuned with dose, dose rate, and temperature as demonstrated in this work. This is ideal for medical applications as the use of ionizing radiation eliminates toxicity concerns and provides simultaneous sterilization of the material.
RESUMO
Reaction of highly soluble orally active, non-peptide antihypertensive drug losartan with copper(II) leads to the spontaneous formation of a very insoluble 2:1 covalent complex, which self assembles in a hydrophobic supramolecular structure of nanometric dimensions. Thermal analysis showed that Los/Cu(II) complex presents intermediate stability in comparison with its precursors KLos and Cu(OAc)2·H2O. Isothermal titration calorimetry indicated complexation to be a stepwise process, driven by enthalpy and entropy. Zeta potential and DLS measurements showed that it is possible to control the size and charge of nanoprecipitates by adjusting the relative concentration of Los(-) and Cu(II).
Assuntos
Precipitação Química , Complexos de Coordenação/química , Cobre/química , Interações Hidrofóbicas e Hidrofílicas , Losartan/química , Tamanho da Partícula , Varredura Diferencial de Calorimetria , Espectroscopia de Ressonância de Spin Eletrônica , Cinética , Luz , Dinâmica não Linear , Análise de Regressão , Espalhamento de Radiação , Solubilidade , Soluções , Eletricidade Estática , Termodinâmica , Termogravimetria , Titulometria , Água/químicaRESUMO
A etapa principal na ativação e ligação da insulina ao seu receptor é a dissociação dos hexâmeros do hormônio, normalmente presente nas preparações farmacêuticas, para a forma monomérica bioativa. A utilização de diferentes ciclodextrinas (CDs) como adjuvantes em formulações contendo insulina vem sendo explorada e os estudos realizados demonstram que estas substâncias podem aumentar a absorção da insulina principalmente por diminuírem sua capacidade de formar dímeros e hexâmeros em meio aquoso. No presente trabalho, complexos de insulina:hidroxipropil-beta-ciclodextrina (INS:HP-beta-CD) e insulina:dimetil-beta-ciclodextrina (INS:DM-beta-CD) foram caracterizados utilizando técnicas de titulação calorimétrica isotérmica e espalhamento dinâmico de luz. Por meio da titulação calorimétrica foram determinados os parâmetros termodinâmicos de interação entre a insulina e as CDs utilizadas, sugerindo que o mecanismo de complexação ocorre com aumento de entropia para ambos os sistemas. Os experimentos de espalhamento dinâmico de luz não indicaram diminuição do diâmetro hidrodinâmico das espécies moleculares de insulina após a complexação com as CDs. Os complexos INS:HP-beta-CD e INS:DM-beta-CD foram encapsulados em microesferas (MEs) de PLGA 50:50. A caracterização das MEs obtidas revelou aumento considerável na taxa de encapsulamento de insulina quando complexada com as CDs sem que ocorresse diferença significativa no diâmetro das partículas em função da complexação.
The main stage in the linking and activation of the specific receptors by the insulin is the dissociation of this peptide hexamers, normally present in pharmaceutical formulations, in the monomeric active form. Because of this, the use of different cyclodextrins as adjuvants in the formulations containing insulin has been explored and the realized studies have demonstrated that the cyclodextrins can increase the absorption of the insulin mainly by reducing the ability of insulin oligomerization in aqueous media. In this work, complexes of INS:HP-beta-CD and INS:DM-beta-CD have been characterized by the use of isothermal calorimetry titration (ICT) and dynamic scattering of light. By means of ICT, the thermodynamic parameters of interaction between insulin and the cyclodextrins have been determined, and it was observed that the complexation occurs with an increase of entropy for both systems. The experiments of dynamic scattering of light have not showed reduction in the size of insulin particles, which could indicate the dissociation of insulin hexamers after the complexation with cyclodextrins. Then, the INS: HP-beta-CD and INS:DM-beta-CD complexes were encapsulated in PLGA microspheres. These systems were characterized and it was not observed any significant difference in the microspheres diameter, but a considerable increase in the hormone loading after the complexation with HP-beta-CD and DM-beta-CD was shown.