| Objective:Cinnamaldehyde was prepared as an oil-in-water submicron emulsion to improve its stability.To screen the optimal prescription of cinnamaldehyde submicron emulsion?CA-SME?and optimize its best preparation process.To prepare and characterize CA-SME,examine its physical and chemical properties and stability.To investigate the anti-arthritis effect of CA-SME on adjuvant arthritis rats,and to study its pharmacokinetic characteristics in rats after oral administration.Methods:The optimal prescription of CA-SME was screened by single factor test.The optimal preparation process of CA-SME was optimized by BBD experiment.The appearance and morphology of CA-SME was observed,and its micromorphology was observed by transmission electron microscope.The particle size,zeta potential and PDI of CA-SME were characterized by particle size analyzer and its stability was investigated.Encapsulation efficiency of CA-SME was measured by ultrafiltration centrifugation.The dialysis bag method was used to study the in vitro release of CA-SME and the release kinetics model was fitted to evaluate its release mechanism.Adjuvant arthritis rats were used as model animals to conduct preliminary pharmacodynamic studies on CA-SME.Pharmacokinetic parameters of rats after oral administration of CA-SME were determined.Results:The optimal prescription of CA-SME was:2.5%CA+1.5%?Tween-80+Span-80?+1.5%MCT+1.5%poloxamer-188+1.5%lecithin+91.5%ultrapure water.The optimal preparation process of CA-SME was:Initial emulsion was prepared by dry glue method and magnetically stirred at 1500r/min for 45min.CA-SME was prepared by high-pressure homogenization method with emulsification temperature of 56?,homogenization pressure of 52 MPa,and 2 homogenization cycles.The appearance of the CA-SME appeared milky white,stable and uniform,without delamination.The microscopic morphology was a regular sphere with average particle size,PDI,Zeta potential,and EE of 257.23±3.74nm,0.157±0.034,-24.78±0.91m V,and 74.47±0.87%,respectively.The in vitro release results showed that the CA-SME release mechanism was first order release kinetics.Compared with the CA solution,CA-SME exhibited sustained slow release,and the drug release percentage was significantly higher than the CA solution,indicating that the preparation of CA into submicron emulsion prevented the oxidative decomposition of CA exposed to air.The stability test results showed that CA-SME has poor stability under strong light?4500LX?and high temperature?40??conditions,the particle size increased,and the absolute value of Zeta potential and encapsulation efficiency decreased.Under the condition of accelerated test?25?±2??and long term test?6?±2??,the stability was good,and all indexes have no obvious change.Therefore,CA-SME should be stored at room temperature or low temperature and protected from light.Pharmacodynamic results showed that CA-SME has anti-arthritis effect on CFA-induced arthritis in rats.Compared with the model group,CA-SME inhibited paw swelling and significantly reduced paw volume?P<0.0001?in arthritic rats.Improved weight loss?P<0.0001?,synovial hyperplasia and inflammatory cell infiltration in arthritic rats.The spleen index and thymus index decreased significantly?P<0.0001?.The level of serum IL-10 was significantly increased?P<0.001?,serum TNF-??P<0.0001?,IL-1?P<0.0001?,IL-6?P<0.0001?and PGE2?P<0.05?levels were significantly reduced.Pharmacokinetic results showed that the pharmacokinetic parameters of CA-SME for oral gavage in rats were Tmax=60min,Cmax=1063.41mg/L,and AUC0-?=113102.61mg/L*min.The Tmax,Cmaxand AUC0-?of CA-SME were 3,3.5 and 2.3 times than that of CA suspension,respectively.Conclusion:The CA-SME prepared in this study has good stability,can improve the bioavailability of CA for oral administration,and has a therapeutic effect on adjuvant arthritis. |
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