| Chitosan is a natural linear polysaccharide composed of glucose structural units.It is non-toxic,non-irritating,non-sensitizing,non-mutagenic,and has good biocompatibility and biodegradability.As a drug carrier,it can control drug release,prolong drug efficacy,and reduce drug side effects.However,chitosan has high crystallinity and poor water solubility,which limits its development.Curcumin is a chemical component extracted from the rhizome of some plants in the family of Zingiberaceae.It has a variety of pharmacological activities,such as anti-inflammatory,anti-oxidation,and anti-proliferation,anti-tumor.However,curcumin is insoluble in water,low in bioavailability,and rapid metabolism in the body.These reasons limit the use of curcumin.Therefore,it is especially important to overcome these problems.There is no research report on the preparation of curcumin chitosan micelles by using modified chitosan micelles as carrier and encapsulating curcumin.This topic intends to modify chitosan to improve its solubility,and to encapsulate curcumin as a carrier to improve the solubility and bioavailability of curcumin.The main research contents of this thesis are as follow: Preparation and optimization of chitosan blank micelles,preparation and optimization of curcumin chitosan polymer micelles,in vitro release studies,carrier and cytotoxicity studies and in vitro experiments of curcumin micelle preparations.Chitosan blank micelles were prepared and characterized.The preparation conditions were further optimized by single factor experiments,and the pH sensitivity was investigated.The optimal preparation condition is that the molar ratio of chitosan to hexahydrophthalic anhydride is 1.6:1.The blank micelles produced under these conditions have good solubility.The resulting blank micelles were pH sensitive and the pH sensitivity point is 5.5.The drug-loaded micelles were prepared and the curcumin was encapsulated to obtain the curcumin chitosan polymer micelles,and the drug loading,encapsulation efficiency and drug release in vitro were investigated.The optimal conditions obtained by single factor experiments are as follow: The optimal carrier concentration was 3.5 mg / mL,the optimal drug concentration was 3.5 mg / mL,and the optimal drug loading ratio was 0.18:1.At this time,the drug loading of curcumin chitosanmicelles was 12.78±0.93%,and the encapsulation efficiency was 89.23±3.31%.In vitro drug release experiments,the cumulative release rate of 72 h was about 30%,with a significant sustained release effect and there is no obvious sudden release.Cytotoxicity test.The cytotoxicity of chitosan blank micelles and drug-loaded micelles was studied with KB and MCF-7 as target cells and calculate the IC50.The IC50 of blank micelles to KB and MCF-7 was 2630±53?g/mL and 780±30?g/mL,respectively.And the IC50 of Cur-loaded micelles to KB and MCF-7 was 34.5±0.15?g/mL and 20±0.012 ?g/mL,respectively.The results showed that the toxicity of chitosan blank micelles was very low,and the drug-loaded micelles had obvious anti-tumor effects.Finally,we study the the tissue distribution of Cur-loaded micelles.The tail vein injection of drug-loaded micelle solution and curcumin injection were performed separately,and the distribution of curcumin was studied in mice heart,liver,spleen,lung and kidney.Compared with the control reagent,the drug-loaded micelles can significantly promote the distribution of CUR in the liver,spleen and lungs,and the elimination rate in plasma and tissues is slowed down,and the residence time is significantly increased,showing good sustained release in vivo.In summary,the chitosan blank micelles prepared successfully in this subject have good solubility,are non-toxic and have pH sensitivity.The prepared Cur-loaded micelle has high drug loading and encapsulation efficiency,and has obvious sustained release effect.There is no obvious burst release,and it can promote the distribution of Cur in the liver,spleen and lung of mice,and the elimination time is slow and the residence time is long. |
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