Preparation And Study On Drug Loaded Of Modified Whey Protein Magnetic Nanoparticles As Drug Carriers

The subject comes from the Chinese Ministry of Science and Technology support project "whey protein application technology research and development"（2013BAD18B07）and Provincial science and technology projects "Key Techniques for Structural Modification and Stability of Collagen Peptide in Rana chensinensis"（3D516CX84071）.Separation of whey protein is of high nutritional value,which is widely used in food and medical applications and has considerable potential for use in drug carriers.In order to improve the clinical application of anticancer drugs,such as side effects and low delivery efficiency,a novel drug carrier system based on modified whey protein magnetic nanoparticles（WMNP）was prepared.And in order to increase the drug loading efficiency of whey protein（WP）,D-xylose was used to bind to WP by glycosylation.Magnetic Fe₃O₄ nanoparticles are provided as targets for this drug carrier system and can be targeted at the tumor site to achieve slow release,allowing the antitumor drug to improve delivery efficiency.Finally,paclitaxel was used as a model drug and coated in the form of microcapsules in a novel drug carrier prepared in this paper to obtain paclitaxel microcapsules with biocompatibility and targeted delivery function.This paper mainly from the following aspects of research and conclusions:WPI and D-xylose,glucose and maltose were used as glycosylation reaction materials,the type of sugar in glycosylation reaction was studied.Doxorubicin hydrochloride and paclitaxel were used as model drugs.Drug and drug release of the impact,mainly on the drug load efficiency of the determination.The results showed that when D-xylose was used as a glycosylation raw material and the hydrophobicantitumor drug paclitaxel was used as a model drug,the drug loading rate of whey protein after glycosylation was higher than that of blank and other sugar,and the loading rate was 93 %.When glucose or D-xylose is a sugar group,paclitaxel is a model drug,the drug can be sustained and stable from the whey protein carrier.The degree of glycosylation,including the degree of turbidity,degree of browning,intermediate product,particle size distribution,zeta potential and the like,of the glycosylation solution were determined by using the drug-handling property,the degree of glycosylation and the physicochemical properties of the glycosylated products.Physical and chemical properties include foaming,rheological properties,viscosity,surface hydrophobicity,etc.,a series of single factor experiments and orthogonal experiments were designed to select the optimal conditions for glycosylation reaction,and thus provide a reliable basis for industrial production.Finally,the Pearson function formula calculated that drug-related and glycosylation degree of the highest correlation,The correlation coefficient P> 0.99,followed by the correlation coefficient between drug loading and surface hydrophobicity was 0.98,indicating that the correlation was high.Finally,the optimum p H was 8,the reaction time was 120 min,The temperature is 70 ° C and the mass ratio is 2: 1.The Circular dichroism（CD）,zeta potential,and scanning electron microscopy showed that the glycosylation reactions occured and reduced the content of whey protein beta-lactoglobulin,etc.,which also changed its original tight structure,so that the structure of whey protein become loose and disorder,can provide a better model for the drug load environment for the follow-up microencapsulation pave the way.（SEM）test showed that the apparent morphology of the glycosylation solution was smooth and delicate,and it had a good application prospect.Fe₃O₄ magnetic nanoparticles were prepared by coprecipitation method and characterized by surface functionalization and characterization.The results show that the magnetic saturation of magnetic nanoparticles prepared by this paper is 70.7 emu /g,which indicates that Fe₃O₄ magnetic nanoparticles have superparamagnetism.The crystal type was measured by X-ray diffraction（XRD）.It was proved that thenanoparticles prepared in this experiment were the stereotactic diffraction peaks of iron oxide with the size of about 19 nm.The Fe₃O₄ magnetic nanoparticles were compared with those of the non-aminated particles by infrared spectroscopy（FT-IR）.The results showed that the absorption peaks at 1620 cm-1 and 1117 cm-1 were found on the spectra of A-Fe₃O₄ nanoparticles due to the N-H bending and C-N stretching modes,demonstrating the successful grafting of amino groups Fe₃O₄ magnetic nanoparticles,this conclusion has a great prospect in the direction of anti-tumor drug carrier,which provides a sufficient theoretical basis for the study of this paper.In this study,the optimal preparation process of microcapsules was determined by using single factor experiment and response surface experiment with the encapsulation rate as the index.The significance level of the response surface model is p <0.0001,so the model can explain the relationship between the factors and the embedding rate.Among the factors,the concentration of xylose and the concentration of calcium chloride had a significant effect on the embedding rate（p <0.01）.There was no significant difference between the other two factors,and the core-to-wall ratio was stronger than the concentration of calcium chloride,the concentration of whey protein and the concentration of whey protein and the concentration of D-xylose.The optimum process parameters were obtained by response surface software: the concentration of whey protein was 15%,the concentration of D-xylose was 25%,the ratio of core to wall was 3:20,the concentration of calcium chloride was 45% The embedding rate of the highest paclitaxel microcapsules was 88%,and the embedding rate of paclitaxel microcapsules was 87.03%,which was less than 1% and the reliability was 99.3% Mimicability.The results showed that the prepared microcapsules had a good appearance,and the hysteresis loop showed that the paclitaxel microcapsules had an appropriate amount of magnetic content.In vitro release study,the results showed that the paclitaxel microcapsules prepared in this study had a p H response and a higher release at a lower p H value,and the release curve was stable within 24 h,which is slow release effect.The above characteristics indicate that the drug carrier prepared in thisstudy has a wide application prospect in the field of anti-tumor therapy.