Preparation and liver targeting of dihydrotanshinone Ⅰ self-microemulsion
Objective To construct a self-microemulsion drug delivery system(DR)for the insoluble natural active substance dihydrotanshinone Ⅰ(DHⅠ),with the aim of improving the solubility of DHⅠ and enhancing its certain passive liver targeting capabilities.Methods Using the solubility of the drug as an indicator,the types of oil phase,emulsifiers,and co-emulsifiers were preliminarily screened.Then,through the drawing of pseudo-ternary phase diagrams and the optimization method of star point design-response surface,the optimal prescription for DR was selected.Subsequently,the morphology of the DR was characterized,its in vitro release was examined,its stability was evaluated,and its liver targeting and intestinal retention was studied.Results The optimal prescription composition of DR was DHⅠ 3 mg(0.1%),medium-chain triglycerides 614.4 mg(20.5%),polyoxyethylene hydrogenated castor oil 944.1 mg(31.5%),and PEG400 1438.6 mg(48%).DR was a red clear solution at room temperature with a drug loading of(1.240±0.014)mg/ml and the solubility of DHⅠ(40 ng/ml)was significantly was improved.After water was added,DR formed a microemulsion system with a light blue opalescence.The results from TEM observation revealed that the particles were uniform spherical shapes.Particle size measurements by a particle size analyzer showed a particle diameter of(104.50±0.45)nm,polydispersity index(PDI)of 0.241±0.004,and Zeta potential of(-10.600±0.462)Mv.In vitro release results showed that compared to the raw DHⅠ,the release rate and cumulative release rate of DR were increased by 3-4 times,and different dispersion media and dilution multiples(20-1000 times)had no significant effect on the particle size and PDI of the formed microemulsion system.After being stored at room temperature for 3 months,there were no significant changes in the appearance,particle size,PDI,and content of DR to indicate its good stability.In vivo distribution studies showed that DR exhibited significant liver targeting and intestinal retention as compared with the raw material.Conclusion The self-microemulsion drug delivery system for DHⅠ is simple to be prepared with stable nature.The system significantly enhances the solubility and release rate of DHⅠ,and possesses liver targeting and intestinal retention properties.This can provide a theoretical basis for the use of DR in the treatment of liver diseases.
dihydrotanshinone Ⅰself-microemulsion drug delivery systemstar point design-response surface methodliver targetingintestinal retention
NETL
NSTL
万方数据
