| Natural polysaccharides are very suitable candidates for the design of novel biomaterials,because they are renewable,nontoxic,biodegradable and excellent biocompatible materials,meanwhile,due to its good degradation efficiency and won’t cause pollution to the environment,large amount of literatures have reported polysaccharides as drug delivery vectors in biomedical area.However,natural polysaccharides are unable to meet the requirements of practical applications,such as unable to load drug,unable to respond to pH changes and the respond to temperature,and unable to deliver the cargo to the desired site,etc.Therefore,more and more attentions have been paid to the modification of natural polysaccharides.The requirements are rigorous,especially for drug and biomacromolecule delivery.The current available carriers may be several characteristics,such as biodegradability,biocompatiblity and low toxicity.Moreover,the methods of modification are complex and the organic solvents are toxic,etc.How to get the modified materials based on polysaccharides by the simple and environmentally methods,and design the drug carriers based on modified polysaccharides requiring further research.Based on the above facts,we successfully designed and synthesized a series of Nanometer microcapsule based on natural polysaccharides possession with pH-responsive property and screen it.And the grafting rate of modified sodium alginate was the highest and the effect of encapsulation and sustained-release was the best.The performance of the modified sodium alginate was discussed,especially on the biocompatibility and the sustained release of VD3.In particular,the preparation of the modified polysaccharides was prepared by using the water as the reaction solvent and synthesized by direct esterification.The main research contents and conclusions are as follows:1、Firstly,Boc-histidine was used as the basic wall material and modified by ultrasonic assisted esterification with seven kinds of polysaccharides:Konjac gum,Pectin,Carboxylate chitosan,Sodium alginate,Carboxymethyl chitosan,β-cyclodextrin and Chitosan.Seven kinds of Boc-histidine polysaccharide nano-microcapsules with excellent properties were prepared,and one kind of nano-microspheres with good modification effect,high embedding rate and good slow-release effect was screened out.The determination of nitrogen content of the synthetised products was measured by element analysis.The optimum synthesis conditions of Boc-histidine-polysaccharide modified substance determined were by single factor experiment,and the response surface methodology was used to optimize the conditions.Main functional groups were characterized by infrared spectrum which used to infer the synthetic route of Boc-histidine-polysaccharide modified substance.The structural change and thermal stability of the products were explored through thermogravimetric analysis(TGA),fluorescence analysis,XRD analysis,xheological mechanics analysis and scanning electron microscopy(SEM).2、Under the ultrasonic condition,the Boc-histidine-polysaccharide modified substance can spontaneously form nanoparticles,and the influence of environmental factors on the stability of nanoparticles was studied by using the particle size and distribution coefficient(PDI)of nano-microcapsules as parameters.The mechanism study showed that Boc-histidine polysaccharide modified substance formed a compact spherical structure by hydrophobic force,hydrogen bond and ionic bond during ultrasonic dispersion,which resulted the good thermal stability,gastrointestinal stability and storage stability.3、Boc-histidine-algin was used for encapsulating VD3 availably and the encapsulation rate reached 89.77%,the Load rate reached 15.27%;the average diameter of nanocapsule were 251.2-275.0 nm,and polydispersity index was all between 0.275 and 0.378.The VD3 and VD3-nanocapsule were stored for 35 days under the condition of high temperature,illumination,and food additives respectively to observe the PRP retention rate,which can determine the protective effect of nanocapsule on VD3.The results showed that the nanoparticles of glycosylation product can protect and improve its thermal stability effectively.82.6%after 35 days storage at 60℃,87.1%after 35 daysstorage at 25℃,and 90.8%after 35 days storage at 4℃.The retention rate did not change significantly when sodium benzoate and potassium sorbate were added,The VD3 can be protected Boc-histidine-algin,which based on theirs antioxygenic property and physical shielding effect.4、Using VD3 as slow-release model,Boc-histidin-sodium-alginate nanocapsules containing VD3 were tested for simulated slow release in oral,intestinal and gastric juice.It was found that VD3 could be effectively protected from pepsin and α-amylase digestion in gastric juice and saliva.Release can be effectively controlled in intestinal fluid.Because Boc-histidine was coated with water-soluble polysaccharides,the sugar chain formed a shell and the hydrophobic part was encapsulated in the nucleus.This structure can effectively embed VD3 and improve its dissolution in water.Because of the good stability of the modified wall material,it can protect the effective substances in the nucleus from being affected by the external environment.The effects of temperature,pH and other factors on the effect of slow release were investigated. |
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