| Resveratrol(Resveratrol,Res)is natural polyphenols with a strong biological activity.It is not only tumor chemopreventive agent,but also is the chemopreventive agent of reducing platelet aggregation,and prevention and treatment of atherosclerosis,cardiovascular and cerebrovascular diseases.Is listed as one of the 100 most popular and effective anti-aging substance.Resveratrol has a strong physiological activity,but because of the poorly water soluble,easy to oxidative decomposition,having rapid metabolism in the body,which greatly restrict itsr in vivo bioavailability.Therefore,the key issues need to be resolved in resveratrol applications are to improve the water solubility of resveratrol,increase its oral absorption,and enhance its bioavailability.In recent years,nanoparticle drug delivery system is a new formulation technology.It not only to increase the solubility of poorly soluble drugs,to improve the bioavailability of drugs in the body,but also has targeted,sustained-release characteristic to make the nanoparticles enhance the drug stability and efficacy and reduce side effects,etc.This topic is based on Res own characteristics,preparing Res nanoparticles formulations by emulsion crosslinking.These nano-preparations make Res water-soluble better,thereby increase the drug bioavailability in vivo,enhance the oral absorption,and improve the efficacy of the drug.The topic first use carboxymethyl chitosan(CMCS)as a drug carrier and utilize emulsion crosslinking method to prepare the resveratrol loaded carboxymethyl chitosan nanoparticles(Res-CMCSNPs).Then through the single factor experiment to optimize the Res-CMCSNPs preparation process,and evaluate its in vitro and in vivo characteristic.The main contents and results are as follows:1.We using the biodegradable material carboxymethyl chitosan(CMCS)as the carrier to prepare Res-CMCSNPs by emulsion crosslinking method;the particle size,potential,drug loading and encapsulation efficiency of the nanoparticles was evaluated to study the impact of preparation process factors on the quality of the preparations;Res-CMCSNPs morphology were investigated by optical microscopy and scanning electron microscopy;the chemical changes of the drug in the preparation of nanoparticles process were research by infrared;the state of presence of the Res in the nanoparticles was analyzed using differential scanning calorimetry(DSC)and X-ray diffraction(XRD).Preparation of an optimal condition is obtained by experiment:the concentration of CMCS was 5mg/ml;Water:chloroform(v:v)?10:1;the ratio of tween 80 was 1/1000;homogenate time was 5min;the pressure of high pressure homogenization was 600ba;number of times of high pressure homogenization was 6 time;anhydrous CaCl2 concentration was 5mg/ml;the lyoprotectant was 5%mannitol.Under this optimal conditions,we prepared Res-CMCSNPs and measured the average particle size was(155.3 ± 15.2)ru;potential was(-10.28 ± 6.4)mv;drug loading was(5.1 ± 0.8)%;ncapsulation efficiency was(44.5 ± 2.2)%.Through the microscope and the electron microscope,the Res-CMCSNPs prepared under optimum conditions was spherical and has uniform particle size distribution and an average particle size was about 200nm.FTIR,DSC and XRD showed that Res molecular morphology was wrapped in the nanoparticles.2.We comparatively studied in vitro antioxidant activity of the Res original powder and Res-CMCSNPs by examining DPPH radical and ABTS radical scavenging ability.The experiments show that,the two radical scavenging ability of Res-CMCSNPs were better than the Res original powder.The nanoparticles improved Res poorly soluble,so that the antioxidant activity of the drug greatly improved.3.We made in vitro release experiments of Res and Res-CMCSNPs through simulating the human gastrointestinal tract in vivo environment.The results showed;the original Res powder due to poor water solubility,failed completely dissolved.The release curve showed a trend of slow release after 2h,and the cumulative release percentage reached only about 65%at 68h.Res-CMCSNPs rendered a good releasing effect;it reached about 80%of the maximum cumulative release percentage at 44h,which was higher than the original powder of Res.With the origin8.0 curve fitting software function,we found that the drug release characteristics correspond to a release of the power model thus more proofed the Res-CMCSNPs had sustained release characteristics.4.In the pharmacokinetic studies of rats,we used HPLC to detect Res content in rat plasma.3P87 pharmacokinetic processing software was used to process data after Res original powder and Res-CMCSNPs were fed to rats,and then we determined the optimal atrioventricular model and calculated pharmacokinetic parameters.In pharmacokinetics process,Res original powder and Res-CMCSNPs were in line with the single-chamber model.Compared with bulk drugs group,nanoparticle group increased in vivo absorption,prolonged duration of action,and the relative bioavailability was increased 3.516 times more than the original powder.Through the above experimental results,we proved the prepared Res-CMCSNPs had uniform particle size distribution,shapeed rules spherical.The drug loading and encapsulation efficiency had achieved the desired results,their physical and chemical properties were stability,and had a certain degree of sustained-release function.Res original powder poorly soluble characteristics was significantly improved,thus improving its bioavailability. |
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