Synthesis And Modification Of Superporous Hydrogels And Study Of Release Properties Of Berberine Hydrochloride

Dispersion polymerization in foam state is a common method preparingsuperporous hydrogels, which have been used in the field of drug release by manyresearchers.Besides, in order to improve the shortcoming of superporous hydrogels’strength, interpenetrating polymer network （IPN） technology is used to increase thestrength of the hydrogels. So hydrogels have better aplication and can achieve thesustained release of drugs.In this paper, P（AA-co-DMAA） copolymerization hydrogel was prepared bydispersion polymerization in foam state,and then P（AA-co-DMAA）/SA compositehydrogel was prepared by IPN technology. The morphology, strength and swellingproperties of two hydrogels were studied and compared. Berberine hydrochloride wasembeded into hydrogels, and the influence of different synthesis conditions andrelease environment on drug-loaded hydrogels’ release properties was studied. Therelease curves were fitted by kinetic models to investigate release kinetics ofdrug-loaded hydrogels. The main contents and results of this paper are summarized asfollows:The superporous copolymerization hydrogel was synthesized by dispersionpolymerization in foam state with acrylic acid （AA） and N,N’-dimethyl acrylamide（DMAA） as monomers, N, N’-methylenebisacrylamide （MBA） as crosslinking agent.Then sodium alginate （SA） as the second network was added to the system, andP（AA-co-DMAA）/SA IPN hydrogel was formed. The FT-IR spectra showed that IPNhydrogel was prepared successfully because of the-COO-asymmetric stretchingpeaks of SA at1608cm-1and1416cm-1. The compressive strength ofP（AA-co-DMAA） and P（AA-co-DMAA）/SA hydrogels of n（AA）:n（DMAA）=1:1were44g/cm2and177g/cm2, which showed that the strength was greatly improved byIPN technology. The SEM spectra showed that P（AA-co-DMAA） had superporousstructure.The pore size of n（AA）: n（DMAA）=1:2hydrogel could reach240μm, andthe pores were blocked and distributed unevenly after interpenetrating.Discussing the impact of different solution on the swelling properties. The studyshowed that the ESR of the two hydrogels gradually decreased with increasing concentration of NaCl solution. With increasing pH value, the ESR ofP（AA-co-DMAA） hydrogel increased first and then decreased. Besides,the greater thecontent of AA, the greater the ESR. With increasing SA concentration, GAconcentration and reaction time, P（AA-co-DMAA）/SA IPN hydrogel’SR decreased.The swelling behavior of copolymer hydrogel and IPN hydrogel showed that IPNhydrogel’s SR greatly reduced comparing to the P（AA-co-DMAA） hydrogel.P（AA-co-DMAA） drug-loaded hydrogels A and B were prepared by adsorptionand embedding. The SEM spectra showed that the monomer ratio of1:3drug-loadedhydrogels A and B retained interconnected porous structure. The SEM spectra ofP（AA-co-DMAA）/SA drug-loaded hydrogels showed that the structure became moredensely and the pore size became smaller with increasing SA concentration, GAconcentration and reaction time. The fluorescence microscopy figure of drug-loadedhydrogels showed that yellow-green fluorescence was observed. The drug distributedevenly in the hydrogels.In different types of solution, drug-loaded hydrogel B was still releasing in8hwhen the drugs of drug-loaded hydrogel A were almost released completely in2h.The release rate of n（AA）:n（DMAA）=1:2drug-loaded hydrogel was the fastest, andn（AA）:n（DMAA）=1:1drug-loaded hydrogel’s was the slowest. The release curve ofn（AA）:n（DMAA）=1:1drug-loaded hydrogel A was fitted in pH=6.8PBS. The resultsshowed that R2value was0.99385by Logistic kinetic equation and was very close to1. It indicated that the Logistic kinetic equation could well describe the releasecharacteristic of drug-loaded hydrogel A. The release curve of n（AA）:n（DMAA）=1:1drug-loaded hydrogel B was fitted in pH=6.8PBS using Sinclair-Peppas kinetic,Logistic kinetic and Sweibull kinetic equation. Fitting R2values were0.99953,0.99967and0.99972, respectively. It showed that the three models’ fitting resultswere good.Compared to P（AA-co-DMAA） drug-loaded hydrogel, drug release time ofP（AA-co-DMAA）/SA IPN hydrogel increased significantly,which was still releasingat24h and had sustained-release effect. The cumulative release rate of the monomerratio of1:1hydrogel almost reached balance at3h and was only7.3%at24h indistilled water, which could reach45.3%and49.2%at24h in pH=1HCl solution and pH=6.8PBS. The release rate decreased with increasing SA concentration, GAconcentration and reaction time. The release rates in order in different solutions wereCaCl₂>MgCl₂>BaCl₂, NaOH>NaH₂PO₄>NaCl. The release curve of n（AA）:n（DMAA）=1:1,4%SA and0.8%GA drug-loaded hydrogel was fitted in pH=6.8PBS using Sinclair-Peppas kinetic and Sweibull kinetic equation. Fitting R2valueswere0.99863and0.99905, respectively, and fitting results were good. The fittingresults of release curves in a variety of other conditions showed that Logistic kineticand Sweibull kinetic equation fitted better and stable.