| In recent years,chitosan calcium alginate(Ca-Alg/CS)gel microspheres have been used as a protein-based oral administration carrier because of their excellent biocompatibility,biodegradability and controlled substance transport.As a micro-scale spherical carrier,the size of microspheres not only affects drug release behavior,but also is an important factor in determining the mode of drug administration.In previous studies,there are few reports in the effect of size-related Ca-Alg/CS microspheres on the structure and controlled release properties.In this paper,based on the preparation of microspheres,the mechanism of the factors affecting the size and morphology of microspheres was investigated.Three different molecular weight molecules were used as "diffusion" model molecules to evaluate the correlation between size and gel structure of Ca-Alg beads.Chitosan was used as"diffusion+reaction" model molecule to study the effect of size and structure on the diffusion and reaction properties of Ca-Alg/CS microspheres.Transform infrared spectroscopy,thermogravimetry analyzer,X-ray diffraction and laser confocal microscopy were used to characterize the gelation of microspheres.Rats with type I diabetes induced by alloxan was used as animal model to investigate the drug release behavior of Ca-Alg/CS microspheres loaded with insulin under the action of size and structure,which not only provids theoretical basis and experimental basis for the application of the ball in the field of medicine,but also expands Ca-Alg/CS gel microspheres in biomedicine and other fields.The main conclusions are as follows:(1)The main factors influencing the size of Ca-Alg beads in high voltage electrostatic field include electric field distribution,output voltage,flow rate,ionic strength and surface tension of solution.Among them,the electric field distribution,output voltage and ionic strength can significantly affect the formation of the liquid cone flow diameter and fracture mode.The output voltage has the most significant effect on the size of beads.The liquid flow and surface tension have the most significant effect on the monodispersity of beads.(2)Molecules with different molecular weight vitamin B12(VB12,1.3 kDa),lysozyme(LZM,14 kDa)and bovine serum albumin(BSA,67 kDa)were used as "diffusion" model molecules and Ca-Alg beads with various diameters(809 ?m,413 ?m,202 ?m)were as abjects to evaluate the correlation between the size and gel structure of Ca-Alg beads.The results showed that the diffusion rate of the model molecules in different sizes of Ca-Alg beads is V809?m>V413?m>V202?m.When the diameter of the Ca-Alg beads is constant,the diffusion rate of the three model molecules is VVB12>VLZM>VBSA.It is shown that with the decrease of the diameter of Ca-Alg beads,the gel structure tends to be dense.(3)Chitosan was used as "diffusion+reaction" model molecule to study the effect of beads size and structure on the diffusion and reaction properties of gel beads.X-ray diffraction and laser confocal microscopy were used to characterize the gelation of the gel.The results showed that the diffusion and film-forming reaction of CS in Ca-Alg beads are scale-dependent.Compared with the large Ca-Alg/CS microspheres,the surface of the smaller microspheres is thicker,the structure is more dense and the stability is stronger.(4)The entrapment efficiency of insulin in Ca-Alg/CS microspheres with 136 ?m,202 ?m,413 ?m and 809 ?m were 52.03%,56.58%64.36%and 66.50%.The cumulative release rates were 64.35%,67.73%,72.80%and 79.91%,respectively.The results showed that under the synergistic effect of size and gel structure,with the decrease of Ca-Alg/CS microspheres size,the release rate of insulin decreased and the sustained release of insulin was better.(5)Rats with type I diabetes induced by alloxan was used as animal model,the freeze dried microspheres with 809 ?m,413 ?m,202 ?m and 136?m loaded insulin were orally administered to rats,the mean relative levels of blood glucose of rats were 80.02±2.99%,67.71±1.74%,45.51±3.51%and 39.92±3.37%,respectively.The relative utilization of pharmacology was 5.42%,11.69%,18.60%and 19.63%.Ca-Alg/CS microspheres of 136 ?m were the most effective,and the blood glucose level was maintained for 10 h,indicating that alginate microspheres can protect insulin by oral route,and the drug bioavailability is higher in smaller Ca-Alg/CS microspheres carriers. |
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