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Studies on Albumin Nanoparticles Drug Delivery System of Curcumin

Author: ZhangHua
Tutor: ZhangLiangZuo
School: Chongqing Medical University
Course: Pharmacy
Keywords: Curcumin Albumin Nanoparticles Pharmacokinetic Tissuedistribution
CLC: R285.5
Type: Master's thesis
Year: 2012
Downloads: 24
Quote: 0
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Abstract


Curcumin (Cur), a yellow natural polyphenol extracted from turmeric (Curcuma longa), has potent anti-cancer properties as has been demonstrated in various human cancer cells. It is a low-molecular-weight natural polyphenol present in turmeric with low intrinsic toxicity but a wide range of antitumor activities. It is a good prospect of anti-cancer drugs. Despite its promising anti-cancer properties, the extremely low water solubility of Cur limits its bioavailability and clinical efficacy.In recent years, nanoparticles drug delivery systems research made a lot of progress. Nanoparticles drug delivery systems are usually made of natural or synthetic polymer materials. It will increase drug absorption, controll drug release, improve drug bioavailability, reduce drug toxicity and increase targeting, especially show advantages in addressing of poorly water-soluble drugs. It offer a new track of poorly water-soluble drugs and large doses of i.v. drug. But due to the materials of the Nps will have a greater toxic effect on the final preparations. We need to consider to the use of low toxic, endogenous or bio-degradation of the physiological compatibility materials, Such as albumin, gelatinum, polyactic acid and so on. Albumin as endogenous substances, with characters of non-toxic, non-immunogenic, can be biodegradable and biocompatibility. It is an ideal material of drugs in targeting delivery system.In this study, we described the Cur-loaded using nanoparticle albumin-bound (nab) technology and desolvation technique. And both studied on the in vitro release and in vivo pharmacokinetics of a preliminary investigation.Part I Study on Albumin Nanoparticles Drug Delivery System of Curcumin using nanoparticle albumin-bound (nab) technologyUV method of Cur was developed for assay. The regression equation was A=0.1721C+0.0075, r=0.9999, which was linear over the range of0.5～6.0mg·mL-1. Its precision, recovery all met the requirement of technology. The result showed that using UV method to determine the Curcumin concentration in vitro was easy, convenient and correct.The prescription of Nab-Cur-BSA-Nps was optimized, the optimized prescription was as follows:oil phase/water phase(1:4, v/v), the concentration of BSA is1%(w/v), the initial content of Cur is2.5mg. The appearance of the form of nanosuspension was observed by cutting microscope and the average particle size was measured by a Malvern Zetasizer Nano ZS90(Malvern Instruments Ltd., Malvern,UK). The lyophilized nanosuspensions showed good redispersibility and the reconstituted nanosuspensions, which saline were orange, colloidal solution. The mean diameters of Nab-Cur-BSA-Nps changed to240.3nm from245.2nm after lyophilization.The distribution of particle size was uniform. The encapsulation efficiency was (42.39±0.91)%(n=3).Dialysis method was used to evaluate the dissolution of Cur from nanosuspensions. In vitro release study revealed that the72h accumulative release percentage reached96%. HPLC method was established to investigate curcumin concentration of plasma and tissue in rats and mice.In this study, Nab-Cur-BSA-Nps were successfully prepared with simple, feasible preparation technology and ease of scale-up. Nab-Cur-BSA-Nps changed because of the formulation of nanosuspensions. Curcumin encapsulated in BSA could improve drug accumulation in lung, extend retention time of drug in the lung, enhance local Curcumin concertration in the lung and improve the therapeutic efficiency. In addition, the side effects in non-target tissues could be avoided and the medication effects could be improved which accompany by good social and valuable Nanoparticles Drug Delivery System of Curcumin.Part II Study on Albumin Nanoparticles Drug Delivery System of Curcumin using desolvation techniqueUV method of Cur was developed for assay. The regression equation was A=0.1721C+0.0075, r=0.9999, which was linear over the range of0.5～6.0μg·mL-1. Its precision, recovery all met the requirement of technology. The result showed that using UV method to determine the Curcumin concentration in vitro was easy, convenient and correct.The prescription of Des-Cur-BSA-Nps was optimized by Single-factor test, the optimized prescription was as follows:the concentration of BSA is1%(w/v), the initial content of Cur is4.0mg, the glutaraldehyde is0.5%×50μL. The encapsulation efficiency was (92.60±0.38)%(n=3).The average particle size was measured by a Malvern Zetasizer Nano ZS90(Malvern Instruments Ltd., Malvern, UK).The mean diameters were316.6nm. The lyophilized nanosuspensions with sucrose showed good redispersibility and the reconstituted nanosuspensions with saline were orange, colloidal solution with mean diameters314.6nm.Dialysis method was used to evaluate the dissolution of Cur from nanosuspensions. In vitro release study revealed that the24h accumulative release percentage reached85%. HPLC method was established to investigate curcumin concentration of plasma in rats.

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CLC: > Medicine, health > Chinese Medicine > Of Pharmacy > Pharmacology > Chinese medicine Experimental Pharmacology
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