Parallel Comparative Studies On Structure And Property Of Alginate Gels With Different Metal Ion Crossliners

In recent years,as carriers of immobilization,alginate microcapsules have attracted great attention in field of drug controlled release.Due to the low mechanical strength and poor control release ability of calcium alginate（Ca-Alg）gels,researchers are also interested in other metal ions(M²⁺)that could crosslinked with alginate.However,the mechanism of the formation of gels crosslinked by M²⁺and alginate has not been further studied.And the relationship between crosslinking mechanism,gel structure and controlled transport properties were also lack of clear understanding.Due to different crosslinking mechanisms with sodium alginate（SA）,alginate gels with significant different structure and properties can be formed by crosslinking with different M²⁺.Based on the valence bond theory,the mechanism of Ba²⁺,Zn²⁺,Ca²⁺crosslinked with SA were analyzed in this paper.The microspheres of barium alginate（Ba-Alg）,zinc alginate（Zn-Alg）and calcium alginate（Ca-Alg）were prepared,and the relation of coordination mode,micromorphology,metal content and thermal stability of the M²⁺crosslinked gels with the structure were characterized by fourier transform infrared spectrometer（FTIR）,scanning electron microscopy（SEM）,inductively coupled plasma-optical emission spectrometer（ICP）and thermogravimetic analysis（TGA）,respectively.As a model protein,bovine serum albumin（BSA,Mw=67 kDa）investigated the diffusion behavior of alginate gels.Making Chitosan（CS,Mw=100 kDa）as a‘diffusion+reaction’model molecule to study the alginate gels structure affecting the diffusion and reaction properties.The drug release behavior of BSA-loaded Ba-Alg/CS gel,Zn-Alg/CS gel and Ca-Alg/CS gel in the simulated body fluid environment was studied.As a model,L929 cells evaluated the biocompatibility of alginate microspheres.It provides the theoretical basis and experimental support for the application of alginate gels to drug controlled release and other fields.The main conclusions are as follows:（1）According to the hybrid orbital theory,we found that Ba²⁺,Zn²⁺,Ca²⁺are hybrid coordinated with SA by means of sp³d²,sp³ and dsp²,forming the different configurations of octahedron,tetrahedron and planar square,respectively.By the analysis of FTIR,the coordination of Ba²⁺,Zn²⁺and Ca²⁺with SA molecules were coexisted by the means of‘pseudo bridged’unidentate coordination and bridging coordination.The gels structure density,metal content,thermal stability and drying rate of Ba-Alg,Zn-Alg and Ca-Alg were decreased successively.（2）BSA were selected as a model protein to investigate the diffusion behavior in alginate gels.In the diffusion equilibrium,the q_t of Ba-Alg gel,Zn-Alg gel and Ca-Alg gel were 0.27 mg·g^-1,0.36 mg·g^-1and 0.46 mg·g^-1,respectively.The results showed that BSA molecules diffusion resistance decreased in order of Ba-Alg gel,Zn-Alg gel and Ca-Alg gel.（3）Making CS as a‘diffusion and reaction’model molecule,with the alginate gel structure more compact,the polyelectrolyte complex membrane（PEM）by CS reacting with alginate was thicker and more compact structure,higher thermal stability,stronger fluorescence intensity and higher membrane stability.（4）BSA as the drug model,the encapsulation efficiency of the BSA-loaded Ba-Alg/CS microsphere,Zn-Alg/CS microsphere and Ca-Alg/CS microsphere was 61.06%,67.43%and70.11%,respectively.The concentration of microspheres in simulated gastric fluid after 2 h were 0.24 mg·m L^-1,0.31 mg·m L^-1,and 0.27 mg·m L^-1,respectively.When the micropsheres transferred to simulated intestinal fluid and release 6 h,the concentration were 0.81 mg·m L^-1,0.90 mg·m L^-1,and 0.97 mg·mL^-1,respectively.Under the effect of the internal structure of the microspheres and the PEM structure,the encapsulation efficiency of Ca-Alg/CS microspheres is highest,but the sustained-release effect of Ba-Alg/CS microsphere is best.（5）The results of MTT experiment show that SA,CS,Ba-Alg,Ca-Alg,Zn-Alg,Ba-Alg/CS,Zn-Alg/CS and Ca-Alg/CS are good materials for biocompatibility,and they can be used in drug controlled release systems.When the concentration of Ba-Alg/CS was less than 2.5mg·m L^-1,it had a promoting effect on cell proliferation.So its biocompatibility was the best.However,the inhibitory effect of Zn-Alg and Zn-Alg/CS on cell proliferation was relatively strong.The average cell survival rate was about 70%,and it had a slight decrease with the increase of concentration.