Preparation, modification, and characterization of alginate hydrogel with nano-/microfibers: a new perspective for tissue engineering.

We aimed to develop an alginate hydrogel (AH) modified with nano-/microfibers of titanium dioxide (nfTD) and hydroxyapatite (nfHY) and evaluated its biological and chemical properties. Nano-/microfibers of nfTD and nfHY were combined with AH, and its chemical properties were evaluated by FTIR spectroscopy, X-ray diffraction, energy dispersive X-Ray analysis, and the cytocompatibility by the WST-1 assay. The results demonstrate that the association of nfTD and nfHY nano-/microfibers to AH did not modified the chemical characteristics of the scaffold and that the association was not cytotoxic. In the first 3 h of culture with NIH/3T3 cells nfHY AH scaffolds showed a slight increase in cell viability when compared to AH alone or associated with nfTD. However, an increase in cell viability was observed in 24 h when nfTD was associated with AH scaffold. In conclusion our study demonstrates that the combination of nfHY and nfTD nano-/microfibers in AH scaffold maintains the chemical characteristics of alginate and that this association is cytocompatible. Additionally the combination of nfHY with AH favored cell viability in a short term, and the addition of nfTD increased cell viability in a long term.

Characterization of N-trimethyl chitosan/alginate complexes and curcumin release.

N-trimethyl chitosan of two quaternization degrees, DQ=20 and 80mol% and labeled as TMC20 and TMC80, were synthesized and characterized by (1)H NMR. Polyelectrolyte complexes (PECs) of TMC/alginate (TMC/ALG) were prepared at pHs 2, 7 and 10 by mixing the aqueous solutions of unlike polymers. The PECs were characterized through infrared spectroscopy (FTIR), thermogravimetric analysis (TGA/DTG) and wide-angle X-ray scattering (WAXS). Using the TMC of DQ=20 mol% and following the same methodology for preparing the PECs, beads of TMC20/ALG were obtained at pH 2 and loaded with curcumin (CUR) at pH 6.0-6.5. The morphology of the beads was evaluated by scanning electron microscopy (SEM). Studies in vitro of the controlled release of CUR from beads were investigated in simulated intestinal fluid (SIF) and simulated gastric fluid (SGF) and treated using conventional and partition-diffusion models. Results indicated that the beads based on TMC20 and ALG presented potential as drug-carrier to improve the solubility and biological activity of CUR at pH close to physiological one.

Preparation and characterization of hydrogels based on homopolymeric fractions of sodium alginate and PNIPAAm.

Graft copolymers were prepared by formation of an amide bond between poly-α-L-guluronic acid (MW 24,000), isolated from sodium alginate and the free amino group of PNIPAAm-NH(2). SEM micrographs revealed the formation of a macroscopic network on the surface of the grafted hydrogels with a porosity diameter of 10-20 µm. Semi-IPN hydrogels were prepared using different proportions of sodium poly-ß-D-mannuronate (MW 21,000), isolated from sodium alginate and cross-linked PNIPAAm-NH(2) polymers. SEM micrographs showed porosities of minor size (∼5 µm). Though both types of hydrogels are good water containers, the water retention capacity of graft copolymers is more than 50% higher than that of semi-IPN hydrogels. Both hydrogel types showed significant changes in swelling ratios between 20 and 45 °C: the swelling ratio decreases near the LCST of PNIPAAm. The water absorption and retention capacity of graft hydrogels increases with pH, reaching a maximum value at pH 7.0.

Formulation and evaluation of carvedilol microcapsules using Eudragit NE30D and sodium alginate

Inclusion complexes of carvedilol(CR) with hydroxyl propyl beta-cyclodextrin (HPBCD) was prepared using co-grinding technique. Then, the inclusion complex was microencapsulated using combinations of Eudragit NE30D (EU) and sodium alginate (SA) utilizing orifice gelation technique. The formulations were analysed by using Scanning electron microscopy (SEM), Fourier Transform Infrared spectroscopy (FTIR), Differential scanning Calorimetry (DSC) and X-ray diffractometer (XRD) and also evaluated for particle size, encapsulation efficiency, production yield, swelling capacity, mucoadhesive properties, zeta potential and drug release. The microcapsules were smooth and showed no visible cracks and extended drug release of 55.2006% up to 12 hours in phosphate buffer of pH 6.8, showing particle size within the range of 264.5-358.5 µm, and encapsulation efficiency of 99.337±0.0100-66.2753±0.0014%.The in vitro release data of optimized batch of microcapsules were plotted in various kinetic equations to understand the mechanisms and kinetics of drug release, which followed first order kinetics, value of "n" is calculated to be 0.459 and drug release was diffusion controlled. The mice were fed with diet for inducing high blood pressure and the in vivo antihypertensive activity of formulations was carried out administering the optimized formulations and pure drug separately by oral feeding and measured by B.P Monwin IITC Life Science instrument and the results indicated that the bioavailability of carvedilol was increased both in vitro and in vivo with the mucoadhesive polymers showing primary role in retarding the drug release.

Prepararam-se complexos de carvedilol (CR) com hidroxipropil beta-ciclodextrina (HPBCD), utilizando a técnica de co-moagem. O complexo de inclusão foi microencapsulado empregando-se associações de Eudragit NE30D (EU) e alginato de sódio (AS), utilizando a técnica de gelificação de orifício. As formulações foram analisadas utilizando-se microscopia eletrônica de varredura (SEM), espectroscopia no infravermelho com Transformada de Fourier, calorimetria diferencial de varredura (DSC) e difratometria de raios X (XDR) e, também, avaliadas por tamanho de partícula, eficiência de encapsulação, rendimento de produção, capacidade de inchamento, propriedades mucoadesivas, potencial zeta e liberação do fármaco. Obtiveram-se microcápsulas lisas e sem fendas visíveis, com liberação prolongada do fármaco de 55,2006% em 12 horas em tampão fosfato pH 6,8, com tamanho de partículas na faixa de 264,5-358,5 mm e eficiência de encapsulação de 99,3337±0,0100-66,2753±0,0014%. Os dados de liberação in vitro de lote otimizado de microcápsulas foram plotados em várias equações cinéticas para se entender os mecanismos e a cinética de liberação do fármaco, que é de primeira ordem, o valor de "n" foi de 0,459 e a liberação do fármaco foi por difusão controlada. Os camundongos foram alimentados com dieta para induzir pressão sanguínea alta e a atividade anti-hipertensiva in vivo das formulações foi obtida por administração de formulações otimizadas e fármaco puro, separadamente, por via oral e medida pelo equipamento BP Monwin IITC Life Science. Os resultados mostraram que a biodisponibilidade do carvedilol aumentou tanto in vitro quanto in vivo com os polímeros mucoadesivos, mostrando papel principal no retardamento da liberação do fármaco.