连翘挥发油纳米胶束对其水溶性成分连翘苷体外透皮、透黏膜吸收的影响

Effects of Forsythia suspensa Volatile Oil Loaded Nanomicellar on Transdermal and Transmucosal Drug Delivery of Phillyrin in Vitro

目的:采用纳米胶束增溶技术制备同时含有脂溶性挥发油与水溶性成分连翘苷(PN)等的全成分载药液体制剂,并考察连翘挥发油纳米胶束对水溶性成分PN体外透皮、透黏膜吸收的影响。方法:采用双提法提取连翘的挥发油与水溶性成分,并用GC-MS测定挥发油的主要成分;再将挥发油以纳米胶束的形式增溶于水溶性药液中制备全成分载药液体制剂(ACLL),采用透射电镜(TEM)、光子相关光谱仪(PCS)与激光共聚焦显微镜(CLSM)考察挥发油纳米胶束的药剂学性质;用高效液相色谱法测定PN含量,采用水平双室扩散池法考察连翘挥发油纳米胶束对PN体外透皮、透黏膜吸收的影响,并与连翘水溶性药液(HCLL)进行对照。结果:连翘挥发油的主要成分为β-蒎烯(49.01%)、α-蒎烯(15.78%)、β-罗勒烯(13.79%)、芳樟醇(5.91%)、α-侧柏烯(2.07%)、β-香叶烯(1.91%)与异松油烯(1.84%)等萜烯类混合物;挥发油胶束为圆球形,粒径为193.3 nm,Zeta电位为-83.8 m V;连翘药液为澄清透明的棕褐色液体,其中PN含量为0.225 mg/m L。实验表明,ACLL组的PN在整个透皮、透黏膜实验过程中的累积透过量始终高于HCLL;7.0 h时,对于透皮给药实验ACLL组PN累积透过量是HCLL组的2.04倍,透黏膜给药实验ACLL组PN累积透过量是HCLL组的1.16倍。结论:连翘挥发油纳米胶束能够促进水溶性成分PN的透皮、透黏膜吸收,体现了其全成分作用的优势,在一定程度上也阐明了中药全成分发挥协同作用的机理之一。

Objective： To prepare all components loaded liquid preparation of Forsythia suspensa（ ACLL） by the technology of nanomicellar solubilization,and to investigate the effects of Forsythia suspensa volatile oil loaded nanomicellar on the transdermal and transmucosal drug delivery of phillyrin. Methods： The volatile oil and hydrosoluble components of Forsythia suspensa were obtained by double extraction synchronously,and the major components of volatile oil were determined by GC-MS. Then the ACLL prepared by the volatile oil was added to the aqueous solution in the form of nanomicellar. The characteristics of ACLL were evaluated by the TEM,PCS and CLSM. The amount of phillyrin（ PN） was determined by HPLC system. The side-by-side diffusion cell was used to investigate the effects of Forsythia suspense volatile oil loaded nanomicellar on the PN transdermal and transmucosal drug delivery,with the hydrosoluble components loaded liquid（ HCLL） used as control group. Results： The Forsythia suspense volatile oil was slight yellowish and transparent liquid with a fragrant odor,the major components as follows β-pinene（ 49. 01%）,α-pinene（ 15. 78%）,β-ocimene（ 13. 79%）,linalool（ 5. 91%）,α-thujene（ 2. 07%）,β-geranene（ 1. 91%）,terpinolene（ 1. 84%）,etc. The Forsythia suspense volatile oil loaded nanomicellar had a closed spherical shape as the TEM and CLSM images appeared. The calculated mean size was 193. 3 nm,the Zeta potential values of- 83. 8 m V. During the whole experiment,the ACLL resulted in a remarkable enhancement of PN transdermal and transmucosal absorption compared with HCLL. At 7. 0 h,the accumulated permeation amount of PN from the ACLL was 2. 04 and 1. 16 folds than that of HCLL for transdermal and transmucosal absorption,respectively. Conclusion： The permeability of PN is obviously enhanced by Forsythia suspense volatile oil loaded nanomicellar for transdermal and transmucosal absorption,these results elucidate the advantages and the mechanism of pharmacological action of all components of traditional Chinese medicine.