Preparation And Pharmacological Evaluation Of Luteolin Nanocomplexes

Luteolin is a natural flavonoid with antibacterial,anti-inflammatory and other pharmacological effects.But its clinical application is greatly limited because it is not easily soluble in water.In this study,by changing the dosage form of luteolin,combined with nano-carrier,to increase the solubility of luteolin.The pharmacodynamics and pharmacokinetic characteristics of luteolin nanocomposites are further evaluated.The development and utilization of new preparations of luteolin provide a more detailed theoretical basis.In this experiment,UV-vis spectrophotometry was used to detect the concentration of luteolin.In the preparation of luteolin nanocomposites,the encapsulation efficiency was used as the index to conduct single-factor investigation to determine the influencing factors;Box-Behnken Design response surface analysis was used to further optimize the prescription;luteolin liposomes,luteolin chitosan and luteolin chitosan liposomes were prepared according to the optimal prescription,and their morphology,particle size,Zeta potential,stability,solubility and hemolysis were investigated.The results show that the three luteolin nanocomposites meet the size requirements of nano-drugs in pharmaceutics,uniform size,good dispersion,slow release effect,good stability,improve the solubility of luteolin and reduce hemolysis.The bacteriostatic effects of three kinds of luteolin nanocomposites on Escherichia coli,Staphylococcus aureus,Trueperalla pyogenes and Streptococcus were determined by cup-plate method.The results showed that three kinds of luteolin nanocomposites had bacteriostatic effect in vitro,and there was no significant change compared with luteolin.The results of pharmacodynamic test in vivo showed that three kinds of luteolin nanocomposites had inhibitory effect on Trueperalla pyogenes in infected mice,could improve the survival rate of mice,and had protective effect on liver and spleen of mice.Luteolin liposome has the best bacteriostatic effect in vivo.In order to explore the pharmacokinetic characteristics of three luteolin nanocomposites in rats after oral administration,the concentration of luteolin in rat plasma was determined by high performance liquid chromatography,and the pharmacokinetic parameters were analyzed by DAS2.1.1 pharmacokinetic software.For luteolin liposomes,T_1/2=16.52 h,T_max=0.75 h,C_max=0.27μg/m L,AUC=9.04μg/m L·h;luteolin chitosan,T_1/2=15.89 h,T_max=0.75 h,C_max=0.28μg/m L,AUC=8.27μg/m L·h;luteolin chitosan liposome,T_1/2=18.50 h,T_max=1.50 h,C_max=0.42μg/m L,AUC=9.78μg/m L·h.The results showed that after intragastric administration,the half-life,peak time and area under the drug time curve of the three luteolin nanocomposites in rats were higher than those of luteolin,which showed slow absorption,slow elimination and high bioavailability in rats.it has a certain sustained release effect,among which luteolin chitosan liposome has the best sustained release effect,which provides guidance for veterinary clinic to make reasonable drug administration plan and drug withdrawal period.To sum up,luteolin liposomes,luteolin chitosan and luteolin chitosan liposomes were successfully prepared to improve the solubility and bioavailability of luteolin.The sustained release effect and pharmacokinetic characteristics of luteolin chitosan liposomes are better than the other two nano-preparations,which are expected to be further developed and utilized.