Study On Transdermal Absorption Bioadhesive Nano-preparation Of Eczema Treatment

Eczema is a kind of skin disease caused by climate change,emotional agitation and external stimuli.Most of the commonly used drugs for local treatment are ZnO or corticosteroids.However,these drugs have the shortcomings of rebound and aggravating of eczema treatment.It was found that the traditional Chinese medicine matrine also has the effect of treating eczema,but the market matrine gels were a common preparation of drugs and gel adjuvants,and it’s weak penetration on the skin surface,which affects the absorption of the drug.On the basis of the original,matrine was used as the target drug,and it was prepared into a nano-scale bioadhesive gel preparation by the combination of emulsifying solvent evaporation and low temperature curing,in order to achieve the prolongation of the residence time of the drug in the stratum corneum.Increase the absorption capacity of the drug.The paper is divided into five parts:The first part is the study on the formulation process of matrine nanoparticles1.Matrine-loaded nanoparticles were prepared via a emulsifying solvent evaporation and low temperature curing.The optimum conditions were investigated by single factor and response surface test using ethanol as solvent.The results showed that the optimal preparation process was emulsifier ratio of 1.7:1 and the ratio of fat to matrine is 12.28:1.The volume ratio of aqueous phase to organic phase is 4.7:1,the emulsification time is46 min,and the emulsification temperature is 70℃.The appearance of the obtained nanoparticles was spherical,The produced nanoparticles were within the nanosized range(164.2±26nm) with relatively low polydispersity index (0.164).The entrapment efficiency of matrine was 73.18% and the drug loading was 1.58%.2.Application of freeze drying technologyThe optimum process of matrine lyophilized nanoparticles was optimized by single factor experiment and orthogonal test.The results showed that the best lyoprotectant was mannitol,added in 5%,The pre-freezing temperature was -80℃ and the pre-freezing time was 18 h.The obtained nanoparticles showed a spherical shape with an average particle size of 259±36 nm.The second part is preparation of matrine nanoparticle bioadhesive nanogel preparation.The preparation process of matrine nanoparticle bioadhesive nano-gel was optimized by single factor experiment and orthogonal test by using tube inversion method and gels were prepared by poloxamer-407 and poloxamer-188 or chitosan,The results showed that the optimal process was:poloxamer-407concentration of 22%,poloxamer-188 concentration of 2%,chitosan concentration of 0.5%,glycerol concentration of 1%,The optimized gel temperature was 34.8℃.The physicochemical properties of the matrine nanoparticle bioadhesive nanogel preparation showed that the gel pH was 6.58,the viscosity was 1.32 pa·s,and the power law showed n<1,indicating that the prepared gel was a non-Newtonian fluid and has the characteristics of shear thinning.The third part is the research of release kinetics of preparation.The release kinetics of the matrine nanoparticle and matrine nanoparticle bioadhesive gel preparation was studied under water,saline solution,pH 5.8.1.The release kinetics of matrine from nanoparticles showed that the matrine nanoparticles could release the drug for up to 48 h.At 48h,the cumulative release was close to 80%,and the release conforms to the first-order kinetic release law.The fitting coefficient(n)<0.45 in the Ritger-peppas model indicates that the drug conforms to the Fick diffusion mode.2.The in vitro release kinetics of matrine nanoparticle bioadhesive gel preparation showed that the matrine nanoparticle bioadhesive gel preparation released about 70%in 48h compared with the matrine gel preparation.The release conforms to the first-order kinetic release law.According to the fitting coefficient(n)<0.45 in the Ritger-peppas model,the drug conforms to the Fick diffusion mode,and the sustained release effect is good.In summary,the release of the nanoparticle preparation has a first-order kinetic release characteristic,which changes the linear release mode of the original matrine material.The fourth part is to establish the quality inspection system and stable experimental study of the preparation.According to the requirements of the Chinese Pharmacopoeia 2015 edition for microparticle preparations and gel preparation,the performance,examination,and content of the gel preparation were established,the influencing factors were tested on the prepared matrine nanoparticle gel preparations.The indexes of the gel composite preparation conform to the requirements of the Pharmacopoeia on gel preperations.The main indicators of the system are:uniform and delicate milky white gel with pH of 6.25~6.58.And the influencing factors test,the preparation is not suitable for storage in a high temperature environment.The fifth part is study on transdermal characteristics of matrine nanoparticle bioadhesive preparation.To investigate the effects of different types and concentrations of penetration enhancers on the transdermal absorption of drugs,and to investigate the skin irritation and hemolysis properties of the prepared bioadhesive gel preparations.In vitro skin penetration study demonstrated that the best penetration enhancer was azone(azetane>borneol>menthol),the best addition was 3%,Qn was 0.40mg/cm~2,and the cumulative transmittance was 49%.The(ER)was 2.41.The skin irritation and hemolysis test results showed that the prepared matrine nanoparticle bioadhesive adhesive preparation was non-irritating and no hemolysis occurred compared with the commercially available preparation.In summary,the matrine nanoparticle bioadhesive gel preparation can release the drug slowly,and has the feasibility of locally delivering matrine to treat eczema.To some extent,it provides new prospects for the treatment of eczema by traditional Chinese medicine instead of chemical drugs.