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Preparation And Evaluation Of Curcumin Inflammation Targeted Self-microemulsion

Posted on:2018-02-27Degree:MasterType:Thesis
Country:ChinaCandidate:L H LiuFull Text:PDF
GTID:2354330515981078Subject:Chinese medicine pharmacy
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Objective:For the cationic proteins are overexpressed on the inflammation of the colonic mucosa,resulting the positive charges of the site of colitis,we built negatively charged self-microemulsifying drug delivery system of curcumin(NC-CUR-SMEDDS)to achieve inflammation targeting.The preliminary evaluation and the pharmacodynamics of the self-microemulsion were discussed in order to provide a new idea for the development of inflammatory targeting formulations and to provide a theoretical basis for the targeted therapy of ulcerative colitis.Methods:On the basis of previous study of CUR-SMEDDS,curcumin was used as a model drug and the optimum amount of excipients was confirmed by the single-factor design experiment taking mean particle size,Zeta potential,drug entrapment efficiency and the drug loadings of curcumin as the evaluation indices for the preparation of NC-CUR-SMEDDS.The quality of NC-CUR-SMEDDS was evaluated by observing its appearance status,morphology of microemulsion and particle size,Zeta potential,drug entrapment efficiency and drug loading.Then ulcerative colitis was induced in BALB/c mice with 5%DSS,the adhesion of NC-CUR-SMEDDS in the inflammatory site was evaluated through ex vivo experiments.At the same time,the drug was delivered directly to the colon site via retention enema administration.Using 5-aminosalicylic acid(5-ASA)as a positive control drug and CUR-SMEDDS as the control group,disease activity index scoring(DAI),colonlength,histopathological score of colonic mucosa,the content of malondialdehyde(MDA),myeloperoxidase(MPO),interleukin-6(IL-6)and tumor necrosis factor-alpha(TNF-?)in colon tissues were investigated to evaluate the therapeutic effect of NC-CUR-SMEDDS in vivo.Results:The optimal formulation of NC-CUR-SMEDDS was Cremophor RH40:Transcutol HP:Capryol 90:Docusate Sodium= 6:3:1:0.4(w/w/w).And it was found that the Zeta potential reached-43.43±0.29 mV when 4%docusate sodium was added.The appearance of NC-CUR-SMEDDS was clear and transparent.Meanwhile the particle size distribution was uniform.The mean particle size was 14.08±0.082 nm,the drug loading of curcumin was 37.98 mg·g-1 and the drug entrapment efficiency was 99.22%.Ex vivo adhesion experiment showed that NC-CUR-SMEDDS preferentially adhered to the inflamed colon mucosa,with a 2.8-fold higher adherence compared to healthy colonic mucosa(P<0.0001).And 1.5-fold higher adherence in inflamed tissue when compared to neutral SMEDDS(P<0.01).NC-CUR-SMEDDS could significantly improve therapeutic efficacy in dextran sulfate sodium induced colitis mice by directly delivering drug to the site of colon through retention enema.As it could relieve the clinical symptoms of dextran sulfate sodium induced colitis mice,including mental status,blood in the stool,body weight and so on.NC-CUR-SMEDDS also relieved the hyperaemia,edema and anabrosis of colon tissue to a certain degree.Histopathological examination result showed that inflammatory cell infiltration reduced and crypt structure was relatively complete,and more calyx cells existed in NC-CUR-SMEDDS group.We also found NC-CUR-SMEDDS significantly decreased the activity of MPO and the content of MDA,TNF-? and IL-6 levels in mouse colon tissue,and the therapeutic effect was close to that of positive control group.Conclusions:It was concluded that NC-CUR-SMEDDS with high entrapment efficiency and uniform particle size distribution met the requirement of inflammatory target binding in the colon and increased the concentration of curcumin in the inflammatory cell surface of ulcerative colitis,which provided new ideas and new methods for the inflammatory targeting drug delivery system.
Keywords/Search Tags:curcumin, negatively charged, self-microemulsifying drug delivery system, targeted drug delivery, ulcerative colitis
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