Preparation And Drug Release Properties Of PH Sensitive Hydrogels

In recent years,smart drug carriers have attracted much attention due to their improved efficiency and activity as well as the reduction of side effects.Oral continuous controlled drug delivery systems are one of the most important challenges facing in the development of new drug.This approach has a number of advantages over traditional dosing modalities,such as reducing dosing frequency,elimination of toxicity and adverse reactions due to overdosing,improving patient compliance,ideal therapeutic drug concentration control,and cost-effective manufacturing.Using biomacromolecules with good biocompatibility to make intelligent hydrogels as drug carriers has aroused the research enthusiasm of researchers.In this paper,two kinds of pH-sensitive hydrogels were prepared by combining potassium humate with gelatin and sodium carboxymethyl cellulose respectively for controlled release of drugs based on the characteristics of non-toxic and harmless potassium humate,good sustained release performance and biocompatibility.The specific research contents are as follows:(1)Using natural macromolecular substances potassium humate(KHA)and gelatin as raw material,acrylamide(AM),2-acrylamide-2-methyl propane sulfonic acid(AMPS)as the monomers,potassium persulfate(KPS)as initiator,N,N’-methylene double acrylamide(MBA)as crosslinking agent,prepared by aqueous solution polymerization method for a kind of chemical cross-linking etc the main pH sensitive potassium humate/gelatin(KHA/Gel/AM/AMPS)hydrogel,the optimum synthesis condition is:the polymerization temperature was 60℃,the dosage of KHA was 0.1g,Gel 1.0g,KPS 0.14g,MBA 0.08g,and AMPS:AM=1:3(AMPS dosage was 2g).FT-IR、SEM、TG、XRD and other testing methods showed that the bond polymerization reaction between KHA,Gel,AM and AMPS occurred successfully,and the hydrogel with three-dimensional network space structure was obtained,and the thermal stability was good.The hydrophilicity,mechanical properties,swelling properties and drug release properties of KHA/Gel/AM/AMPS hydrogels were studied.The results of hydrophilicity test showed that KHA/Gel/AM/AMPS hydrogel had excellent hydrophilicity,which provided strong support for its ability of water absorption and swelling.The test of mechanical properties showed that the hydrogel had good mechanical strength and was not easy to be broken under the action of external force,resulting in the release of a large amount of drugs.The swelling property shows that the hydrogel is sensitive to salt ions and pH.In vitro drug release experiments showed that the release rate of riboflavin was low under acidic conditions(pH=1.2),namely in gastric juice.Under alkaline conditions(pH=7.4),i.e.in intestinal fluid,the release rate of riboflavin was relatively high.The hydrogel swelling process and drug release process were analyzed by mathematical model.It was concluded that the hydrogel swelling was in line with Schotts second-order swelling kinetics,and the drug release mechanism was Fickian transport mode.(2)Combined with potassium humate(KHA)and sodium carboxymethyl cellulose(CMC)molecular structure feature,the molecular design and self-assembly,with KHA and CMC as raw material,the use of CMC and Fe3+easy crosslinking characteristics,Fe3+ as crosslinking agent,the drop ball KHA/CMC-Fe3+ water gel ball,then through self-assembly technology will chitosan(CS)coated in KHA/CMC-Fe3+ water system to get pure physical crosslinking gel ball with a pH sensitive(KHA/CMC Fe3+)@CS hydrogel.The results of FT-IR、SEM、TG and XRD showed that the hydrogel was formed by metal ion coordination between KHA,CMC and Fe3+,and CS was also coated on the surface of the hydrogel sphere in a non-covalent bond way,so the hydrogel sphere with good thermal stability was obtained.The apparent diameter,stability,swelling property and drug release property of(KHA/CMC-Fe3+)@CS hydrogel spheres were studied.The results show that the diameter of wet hydrogel sphere is about 2 mm,and the swelling process of hydrogel sphere has significant pH sensitivity.In vitro drug release experiments showed that the release rate of riboflavin was low in acidic environment(pH=1.2),while the release time was long and the release rate was high in alkaline condition(pH=7.4).The swelling process of hydrogel ball and drug release process were analyzed by mathematical model.It was concluded that the swelling of hydrogel complied with Schotts second-order swelling kinetics,and the drug release mechanism was Fickian transport mode.