Preparation And Evaluation Of Albumin Nanocomplex Containing Astaxanthin

Background: Astaxanthin is a fat-soluble ketone carotenoid,which is mainly extracted from Haematococcus pluvialis.In recent years,a large number of studies have shown that astaxanthin has a strong capacity to antioxidant,anti-inflammatory,anti-cancer,and immunomodulatory.So it has been widely used in medicine,food,and cosmetics industry.However,the application of astaxanthin is limited by its poor water solubility,stability,and low oral bioavailability.Therefore,it is necessary to establish a suitable drug delivery system to improve the water solubility and stability of astaxanthin and increase its oral bioavailability.Objective: Preparing insoluble drugs into nanomedicine could highly improve its water solubility,stability,and oral bioavailability.Albumin is a common protein carrier material which has good biocompatibility and can encapsulate,link,or adsorb drugs,and improve the water solubility of poorly soluble drugs.Based on this,bovine serum albumin(BSA)and PEG-modified bovine serum albumin(PEG-BSA)were selected as carrier materials to prepare astaxanthin albumin nanocomplexs.Methods and Results: The research mainly includes the following three aspects:(1)Preparation and characterization of astaxanthin albumin nanocomplexs;(2)Oral absorption study of astaxanthin albumin nanocomplexs;(3)The application of astaxanthin albumin nanocomplexs on radiation damage protection.(1)Preparation and characterization of astaxanthin albumin nanocomplexs.In this chapter,BSA and PEG-BSA were chosen as drug-carrying materials.Astaxanthin albumin nanocomplexs(ASXNPs)and polyethylene glycol modified astaxanthin albumin nanocomplexs(PEG-ASXNPs)were prepared by an emulsion solvent evaporation method,and the single factor method analysis was used to optimize the formation process.The mean particle sizes of ASXNPs and PEG-ASXNPs were131.16±0.60 and 115.56±13.26 nm,respectively,and zeta potentials were-17.20±0.43and-9.66±0.23 m V,respectively.Further,transmission electron microscope(TEM)showed that the shape of two nanocomplexs was both relatively round.Besides,the encapsulation efficiency of ASXNPs and PEG-ASXNPs determined by HPLC was97.32±0.23% and 98.10±0.48%,respectively.Then the drug-loaded nanocomplexs were characterized by X-ray diffraction and differential scanning calorimetry,We found that astaxanthin could be effectively encapsulated by protein carriers.Moreover,after placing drug-loaded nanocomplexs at 4℃,the stability results showed that the drug content and ABTS free radical scavenging rate did not change significantly,and the drug content decreased slightly after placed in serum for 12 h at 37℃.(2)Oral absorption of astaxanthin albumin nanocomplexs.Firstly,the stability of drug-loaded nanocomplexs in artificial gastric juice and intestinal juice was investigated.The results showed that after incubation of ASXNPs and PEG-ASXNPs in artificial gastric juice and artificial intestinal fluid for 2 hours,respectively,the drug content and ABTS free radical scavenging ability did not change significantly,indicated that nanocomplexs have good stability.Secondly,the rat ligated intestinal circulation model was chosen to investigate the absorption of drugs in the rat small intestine.The results showed that the two drug-loaded nanocomplexs were well absorbed in the small intestine,and the absorption capacity of PEG-ASXNPs in the small intestine was stronger.Finally,with commercially available astaxanthin as a control,the oral absorption of the drug-loaded nanocomplexs in SD rats was investigated.The results showed that the area under the blood concentration-time curve(AUC)of PEG-ASXNPs was 5.57 times and 6.03 times as compared with commercially Bio Astin and Astaxin,respectively,and the AUC of ASXNPs was 2.29 times and 2.48 times as compared with Bio Astin and Astaxin,respectively.So PEG-ASXNPs and ASXNPs could significantly improve the oral bioavailability of astaxanthin.(3)The application of astaxanthin albumin nanocomplexs on radiation damage protection.With the astaxanthin as a control,the ABTS free radical scavenging ability of drug-loaded nanocomplexs was investigated.The experimental results showed that in the concentration range of 10-80 μg/m L,the antioxidant activity of astaxanthin was concentration-dependent.The antioxidant activity of astaxanthin was weak when the concentration was lower than 10 μg/m L,but when the concentration was above 80μg/m L,there was no significant change.The pharmacokinetic behavior of ASXNPs and PEG-ASXNPs in rats and the distribution of tissues in mice were investigated by injecting the drug-loaded nanocomplexs solution via the tail vein.Compared with ASXNPs,the PEG-ASXNPs could extend the circulation time of astaxanthin in the blood,reduce the distribution of astaxanthin in the liver and spleen,and increase the content of astaxanthin in heart,lung,and kidney.A model of radioactive damage in mice was established to investigate the protective effect of PEG-ASXNPs on radioactive damage in mice.The results showed that PEG-ASXNPs could increase the spleen index and thymus index,increase the level of SOD in the peripheral blood,and reduce the level of MDA.Conclusion: Based on the interaction between astaxanthin and serum protein molecules,astaxanthin albumin nanocomplexs were prepared to improve the water solubility and stability of astaxanthin,enhance the astaxanthin absorption in rat small intestine,increase the oral bioavailability of astaxanthin and improve its effect on radioactive damage protection.This study could provide the preliminary experimental basis on the development of astaxanthin nanocomplex.