Dual Responsive Microgels Based On Starch: Preparation And Application

A suitable delivery carrier materials with high loading efficiency and effective controlled release functionality can protect the functional ingredient from being stimulated by gastric secretion. In this work, based on the structural properties of starch granules, noncrystalline, carboxymethylation and cross-linking treatments were adopted as the synthesis of a smart microgel, which had been used in controlling the release of model proteins, model hydrophobic materials and model small molecules.Noncrystalline granular starch and its noncrystalline carboxymethyl starch (CMS) were prepared with the physical method of ethanol-heating treatment. Techniques of Polarizing microscopy, SEM、DSC、XRD were applied to characterize their structure. The results showed that 50%-ethanol could protect starch granules from swelling while thermal treatment was able to destroy crystalline structure of the granules. This granules had granular shape but no crystalline structure. This special structure improved the reaction efficient of synthesis of CMS by 16.1%. Meanwhile a higher of degree of substitution was observed in CMS (DS 0.95) for the noncrystalline granular starch.Microgels with different degree of substitution and crosslinking densities were synthesized using CMS by chemical crosslinking. The linkages of ester group were introduced on the hydroxyl groups of CMS, as detected by the content of phosphorus and FT-IR analysis. The thermal stability of microgel was higher than that of corresponding CMS. The higher degree of substitution (DS) in microgels, the lower thermal stability was. The level of crosslinking by adjusting the molar ratio of sodium trimetaphosphate and CMS (RSTMP/CMS) showed little effect on the thermal stability. As for the particle size of microgels, it had a range of 25-45 μm, which could be increased by higher DS. As for the microgels with higher crosslinking density, their particle size slightly shifted to a smaller trend. An interesting find was that the synthesized microgels were sensitive to the factors of pH and ionic strength. The microgels swell greatly and became more elastic as the pH increased from 3 to 5. An opposite trend was observed in the counterparts of microgels when they were dissolved in higher ionic strength (0.5M). Moreover, the higher DS resulted in higher swelling behavior and elastic modulus (G’) while the crosslinking density had an adversed effect. Another particular interest was observed in the zeta-potential analysis. It exhibited a negative correlation with DS and ionic strength while a positive correlation was indicated on the environmental pH values. There was no significant changed occurred on the different crosslinking densities of microgels. However, the higher DS microgels exhibited a lower Zeta-potential than lower DS microgels did.The electrostatic interactions between the CMS microgel and protein molecules were evaluated, which provided a stable control of uptaking and releasing model proteins (lysozyme). As a result, the loading capacity of microgel increased with increasing DS while the RSTMP/CMS and ionic strength had a negative effect on the loading capacity. A maximal loading capacity of microgels was obtained at 6.92 mg/mg. The lysozyme-microgel complex was identified by confocal laser scanning microscopy (CLSM) since the lysozyme was labeled with FITC. It indicated that the lysozyme distribution was rather homogeneous in the microgel with low RSTMP/CMS. The lysozyme was distributed around the surface area when the microgels had high RSTMP/CMS. As for the effect of DS on the loading capacity of microgels, which could be as a function of fluorescence intensity, an increase of the DS decreased the fluorescence intensity. Furthermore, FTIR and Raman spectrum analysis results suggested that the secondary structure of lysozyme remained unchanged when lysozyme-microgel complex was formed. The control release of lysozyme under in vitro gastrointestinal tract environment confirmed that microgels can be used as carried materials for lysozyme (model proteins). Circular dichroism spectrum analysis results suggested that microgels provided the lysozyme with potential protection in the gastrointestinal delivery system due to the unchanged structure observed in lysozyme.The pH 3 was the optimal pH for loading β-Carotene nanoemulsion droplets at ionic strength 0.02 M. the maximum loading capacity of microgel was 28.3 μg/mg while the RSTMP/CMS and substitution of microgel were 0.1 and 0.67, respectively. The β-Carotene distribution in the microgel was identified by CLSM and suggested that the β-Carotene was distributed around the surface of microgels except for the group of RSTMP/CMS at 0.1.CMS/β-cyclodextrin (β-CD) microgels have been synthesized because β-CDs were capable of including small guest molecules such as ascorbic acid. Most of the synthesized microgels had diameters distributed between 10 and 25 mm. Its thermal stability was a middle state between that of CMS and β-CD. Swelling and rheological results revealed that the CMS/β-CD microgels had a dual responsibility for pH and ionic strength factors. FTIR and DSC data demonstrated the formation of a microgel-ascorbic acid inclusion complex and indicated the maximum loading of ascorbic acid (0.195mg/mg). In vitro release results indicated that the CMS/β-CD microgels mignt potentially be applied as a carrier system to prevent the early release of ascorbic acid in the stomach and target its delivery to the intestine.In this work, the fast-releasing behavior of microgel complex was fixed using a layer-by-layer self-assembly technique. The distribution of chitosan in the microgels was identified by CLSM, and the optimal molecular weight of chitosan was 100kDa which could be absorbed on the microgels surface. The chitosan was as a function of the first while the CMS was used as the second layer. The amount ratio of chitosan and CMS to microgels in the complex were 0.1 and 0.06, respectively. In vitro release results indicated that the double layers complex might potentially be applied as a carrier system to prevent the early release in the stomach and target its delivery to the intestine.