Preparation Of Chitosan/surfactant Aggregates And Drug-loading Studies

The surfactant molecules can self-assemble at certain concentration and formed ordered assemblies including micelles,vesicles,microemulsions,liquid crystals,gels and so on.Among them,lyotropic liquid crystals were widely used in pharmaceutical filed due to its high viscoelasticity,protecting bioactive molecules from hydrolysis or oxidation,potential ability of sustained and controlled release and so on.In this paper,lyotropic liquid crystals were constructed in the mixtures of biocompatible amphiphilic molecules and traditional surfactants as drug carriers to encapsulate drugs.The microstructures and rheological properties of lyotropic liquid crystals were investigated by small angle X-ray scattering and rheological technology at different conditions.Moreover,in vitro release behavior of drugs was further investigated.This paper included the following parts:Firstly,the chitosan-based aggregates were reviewed before the experiment.The aggregates formed in the mixtures of chitosan and surfactants(including anionic,nonionic and cationic surfactants)were expounded systematically,and further demonstrated the research status of chitosan-based aggregates as drug carriers.Secondly,based on the literatures of bile salt,it had potential prospects in field of drug carriers because of its non-toxic,biocompatible,biodegradable and so on.Finally,the application of lyotropic liquid crystals possessed different structures as drug carriers was reviewed.Lyotropic liquid crystals had a good ability to encapsulate hydrophilic and hydrophobic drugs,they can also achieve the sustained release of drugs.Therefore,based on our laboratory research,lyotropic liquid crystals were constructed in chitosan or sodium deoxycholate and surfactants mixtures to encapsulated drugs,further studied the microstructures,rheological properties of drug-encapsulated lyotropic liquid crystals and the release of drugs from lyotropic liquid crystals.The phase behavior of Tween 80/water-souble chitosan/EtOL/H2 O system containing different water-souble chitosan content was investigated at 25 oC.The hexagonal liquid crystal was chosen to encapsulate apigenin.The effect of water-souble chitosan content and temperature on the rheological properties of apigenin-encapsulated hexagonal liquid crystal and the release of apigenin from hexagonal liquid crystal were investigated.The experiment results showed that: 1)After introducing water-souble chitosan,the apigenin-encapsulated hexagonal liquid crystal underwent a transition from viscoelastic fluid to gel-like fluid.The structure of hexagonal liquid crystal became more stable as indicated by higher elastic modulus.The water-souble chitosan can prolonged the release time of apigenin effectively and decreased the release rate of apigenin.2)With increasing water-souble chitosan content,the elastic modulus of hexagonal liquid crystal increased,and the release rate of apigenin decreased,which further confirmed that the water-souble chitosan can enhance the stability of hexagonal liquid crystal and prolonged the release time of apigenin.3)With increase in temperature,the elastic modulus of hexagonal liquid crystal containing high water-souble chitosan content decreased,reflecting weak stability at high temperature.And the release rate of apigenin increased and then decreased.4)The release rate of apigenin from hexagonal liquid crysatl containing water-souble chitosan decreased with increasing the pH value of release medium,which was opposite of that without water-souble chitosan.The release behavior of apigenin followed the first-order kinetic model,indicating a diffusion controlled release.The hexagonal and cubic liquid crystals were constructed to encapsulate curcumin by introducing high NaDC content to Brij 97 system.The effect of oil/water ratio or curcumin content on the rheological properties of curcumin-encapsulated liquid crystals was investigated.The results showed that the elastic and viscous moduli of curcumin-encapsulated hexagonal liquid crystal decreased in following sequence with increasing oil/water ratio,M2Cur3?M3Curs?M4Curs?M6Curs? M5 Curs,M2Cur3?M3Cur3?M4Cur3?M5Cur3 ?M6Cur3.For the hexagonal liquid crystal without curcumin,the moduli increased and then decreased.Moreover,the elastic modulus of hexagonal liquid crystal decreased and then increased with increasing curcumin content,which was consistent with the values of as increased and then decreased.For the cubic liquid crystal,the elastic modulus decreased slightly with increasing curcumin content,which was consistent with the change of as.These results showed different stability of curcumin-encapsulated liquid crystals.The hexagonal liquid crystals constructed in Tween 80/water-souble chitosan/EtOL(sun flower oil,soybean oil)/H2 O system were selected to encapsulate curcumin.The rheological properties of curcumin-encapsulated hexagonal liquid crystal and the release of curcumin were also investigated at different condition such as different water-souble chitosan content,different temperature and so on.The rheological results showed that the water-souble chitosan enhanced the stability of curcumin-encapsulated hexagonal phase as indicated by higher elastic modulus.While the elastic modulus of curcumin-encapsulated hexagonal phase containing high water-souble chitosan content decreased with increasing temperature,reflecting different stability of hexagonal phase.The in-vitro release of curcumin followed the first-order release kinetics,indicating a diffusion controlled release.The release time of curcumin extended and the release rate decreased obviously after introducing water-souble chitosan.With increase in temperature(25-37 oC),the release rate of curcumin increased.Moreover,with increasing pH value of release medium,the release rate of curcumin from the sample containing water-souble chitosan decreased slowly,while the change of pH value of release medium had almost no effect on the release of curcumin from the sample without water-souble chitosan.