| Coenzyme Q10(CoQ10)is an antioxidant which is widespresd in higher plants and animals,it has been found to be effective in cardiovascular diseases and neurodegenerative diseases.COQ10 shows a downward trend after it reaches the peak in the body at 20-year-old,and the content of CoQ10 in old age is decreased by 57%than that of 20 years of age.So the outside supplement of CoQ10 has a positive meaning for maintaining normal metabolism of the human body.However,CoQ10 is not soluble in water,leading to poor absorption and very low bioavailability(2-3%)in the human body,which cannot achieve the desired therapeutic effect and nutritional health benefits.In order to improve the bioavailability of CoQ10,domestic and foreign researchers have done a lot of works.However,there are some problems such as obvious enhancement,poor stability,and uncertain security.Micronized technology can process the raw material into nanoparticles directly.By reducing the particle size,the surface areas of drug particles are increased,resulting in achieve the purpose of improving its water solubility.It dose not employ any organic solvents and carrier material,so security is very high.The main purpose of this project is the use of micronized technology to prepare a new type of CoQ10 nanoparticles,and its physical and chemical characterization,bioavailability,antioxidant activity,and myocardial protection were researched and evaluated,a significant effect water-soluble powder formulation of CoQ10 was expected.In this study,based on the improved rapid expansion of supercritical equipment,analyzing the main factors affecting on mean particle size by the orthogonal experiments,the optimal process conditions to product CoQ10 nanoparticles were developed as follow:dissolved pressure at 25Mpa;solution temperature at 40?;nozzle diameter at 200?m;crystallization temperature at 25?.COQ10 nanoparticles were prepared by a rapid expansion of supercritical process(RESS)with an average diameter of 147.9±27.3nm.At the same time,by LC-MS/MS,X-ray diffraction,DSC differential thermal analysis,laser diffraction and infrared spectroscopy,physicochemical properties of CoQ10 nanoparticles were characterized.solubility and stability study showed that,in comparison with the unprocessed CoQ10 powder,CoQ10 nanoparticles has not changed in molecular weight and chemical structure,but its crystallinity and melting point decreased significantly,which indicates a change in crystalline caused by the rapid expansion of supercritical process.The smaller nanoparticle size and the less crystal structure led to improved solubility and dissolution rate of CoQ10 nanoparticles,and coenzyme Q10 nanoparticles process good physical and chemical stability under room temperature and dark conditions.Bioavailability of CoQ10 nanoparticles was studied by RP-HPLC detection of CoQ10 concentration in rats'plasma after a single oral dose in this issue.Pharmacokinetic parameters of CoQ10 nanoparticles were calculated with unprocessed CoQ10 powder as a reference.The results showed that the bioavailability of CoQ10 nanoparticles is 1.96 times than that of unprocessed CoQ10 powder in rats.Using natural aging model the effect of CoQ10 nanoparticles on rat plasma levels of CoQ10 and antioxidant activity was examined in vivo,with unprocessed CoQ10 and vitamin E powder as a reference.The results showed that with exogenous supplement of CoQ10 nanoparticles,the plasma CoQ10 levels,superoxide dismutase activity,glutathione peroxidase activity were significantly increased,and MDA content was significantly reduced in the plasma of old rats,resulting anti-oxidation ability of the old rats was supper than the normal young rats.The antioxidant activity of CoQ10 nanoparticles is better than the unprocessed CoQ10 powder,but less than vitamin E.The CoQ10 nanoparticles prepared by RESS provided a water-soluble dosage form to research the role of CoQ10 on myocardial protection at the cellular level.The primary neonatal rat myocardial cells were isolated and cultured in vitro,and the hypoxia/reoxygenation model was established to study the mechanism of CoQ10 on myocardial protection.Through the detection of the cell survival,reactive oxygen species,LDH leakage volume,SOD activity,MDA content,mitochondrial membrane potential and cell apoptosis rate,the results showed that in the hypoxia/reoxygenation conditions,CoQ10 can improve the myocardial cells survival,reduce the amount of LDH leakage and the content of MDA in myocardial cells,inhibit the decline of mitochondrial membrane potential,leading to reduce the apoptotic rate of myocardial cells.Howerve,CoQ10 has no significant effect on intracellular ROS levels and SOD activity.From the above results,it can be concluded that the CoQ10 nanoparticles provide a new water-soluble micronized powder dosage form of CoQ10,which can enhance the oral bioavailability and antioxidant capacity of CoQ10. |
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