Study On The Application Of Carboxymethyl Cellulose Based Hydrogel In Drug Delivery System

Soybean peptide（SPE）has many antioxidant properties,such as scavenging free radicals,chelating metal ions and inhibiting lipid peroxidation.It is a natural antioxidant.However,it is difficult for SPE to reach the small intestine during oral delivery,resulting from the effect of the environment of low pH value and ion disturbance in the stomach to SPE.Moreover,it is hard for water-soluble SPE to pass through the stratum corneum skin barrier surrounded by lipids to reach the blood,thus affecting its antioxidant activity.In order to improve the bioavailability of SPE,SPE delivery carrier has become a research hotspot in recent years.Carboxymethyl cellulose（CMC）is the most widely used polyanionic cellulose derivative,owing several valuable characteristics,like good biocompatibility and drug loading.Therefore,it is of great significance to study the ability of CMC-based composite hydrogel to retain the antioxidant activity of SPE in SPE delivery system for expanding the utilization of SPE.In this paper,using CMC as raw material,CMC-based composite hydrogels were prepared by freeze-thaw cycle method and their ability to deliver SPE in different environments was studied.The main conclusions of this paper are as follows:（1）Through the analysis of SEM,BET and MIP,it was found that the CMC/polyvinyl alcohol（PVA）composite hydrogel formed a physically cross-linked porous network structure,and the pores of the hydrogel contracted after loading SPE.FT-IR,XRD and DSC analysis showed that there was hydrogen bonding between CMC and PVA,SPE was successfully loaded in CMC/PVA composite hydrogel and loaded SPE interacted with CMC and PVA by inter-molecular hydrogen bonds and electrostatic interaction.The in-vitro release data showed that the cumulative release of CMC/PVA composite hydrogel which loaded with SPE in simulated gastric fluid without enzyme was less than 5.96%,while SPE could be completely released in simulated intestinal fluid without enzyme,and its release mechanism in simulated intestinal fluid without enzyme followed Super Case-II transport.The released SPE still had antioxidant activity,and the maximum scavenging rates of DPPH and ABTS free radicals were 41.67%and31.43%,respectively.In summary,the CMC/PVA composite hydrogel prepared in this experiment can overcome the low pH value and ion barrier in simulated gastric fluid without enzyme,and has potential application in the delivery of peptides and proteins.In order to further explore the various delivery methods of CMC-based composite hydrogels,this paper will deeply analyze the feasibility of transdermal delivery of SPE based on the study of oral delivery of SPE.The results of PCD,FT-IR and rheology showed that there were chemical and physical cross-linking among CMC,cation starch（CS）and Ca²⁺,forming a stable CMC/CS/Ca²⁺composite hydrogel,and the interaction between loaded SPE,CS and Ca²⁺also occurs such as hydrogen bond and static electricity.SEM and BET analysis showed that there was a porous network cross-linking structure in the CMC/CS/Ca²⁺composite hydrogel,and the pores became small and dense after loading SPE.The release behavior of CMC/CS/Ca²⁺composite hydrogel which loaded with SPE belongs to swelling controlled release type.The maximum cumulative release of SPE was up to 64.23%at 480 min,and the maximum scavenging rates of DPPH and ABTS free radicals of SPE released were as high as 47.07%and72.16%,respectively.The maximum cumulative penetration percentage of SPE is 84.13,92.93and 82.62%respectively.Most of the SPE can successfully pass through the stratum corneum and reach in blood,and its transdermal delivery mechanism follows Fickan diffusion or CaseⅡtransport,which provides an experimental basis for transdermal delivery of peptides and proteins.