粒径对吴茱萸次碱混悬凝胶透皮吸收的影响

Effect of particle size on transdermal absorption of Suspension gel of Rutaecarpine

目的研究药物粒径对吴茱萸次碱(Rut)混悬凝胶透皮吸收的影响。方法采用高速剪切法制备Rut微米混悬液(Rut-MS)和高剪切-高压均质法制备Rut纳米混悬液(Rut-NS),并进行粒径、PDI测定,再制成Rut微米混悬凝胶(Rut-microgel)和Rut纳米混悬凝胶(Rut-nanogel);以SD大鼠皮肤为扩散屏障,采用改良Franz扩散池法进行Rut-microgel和Rut-nanogel体外透皮吸收试验,分别测定2、4、6、8、10、12、24 h的透皮接收液和皮肤滞留液中Rut含量,比较24 h累积透过量(Q_(24))、透皮速率(J_(s))、时滞(t_(lag))及皮肤滞留量(Q_(s))。结果Rut-MS和Rut-NS的粒径和PDI分别为(1317.46±107.27、211.66±1.06)nm;0.367±0.029、0.233±0.011,Rut-microgel和Rut-nanogel中Q_(24)、J_(s)、t_(lag)、Q_(s)分别为(19.5482±4.769、31.8065±4.401)μg/cm^(2),(3.74±0.44、1.76±0.50)μg/cm^(2)·h,16.92、10.68 min,(0.3661±0.2132、0.1692±0.0733)μg/cm^(2),Rut-nanogel的Q_(24)、和J_(s)分别是Rut-microgel的1.62和2.13倍,t_(lag)较Rut-microgel缩短6.24 min,Rut-microgel的Q_(s)是Rut-nanogel的2.16倍。结论Rut粒径减小可以促进Rut混悬凝胶透皮吸收速率,增大透过量,并缩短透过时滞。

Objective The purpose of the study is to investigate the effect of particle size on transdermal absorption of rutaecarpin’s suspension gel.Methods Rut micron suspension(Rut-MS)and Rut nanosuspension(Rut-NS)were prepared by high-speed shearing method and high shear-high pressure homogenization method,and particle size and PDI were measured,and then Rut micron suspension gel(Rut-microgel)and Rut nanosuspension gel(Rut-nanogel)were made.The modified Franz diffusion cell method with SD rat skin as a diffusion barrier was used to conduct Rut-microgel and Rut-nanogel in vitro transdermal absorption.The content of Rut in the transdermal receiving fluid and skin retentive fluid were measured at 2,4,6,8,10,12 and 24 h,respectively.And the cumulative permeation volume(Q_(24)),skin penetration rate(J_(s)),and time lag(t_(lag))at 24 h and skin retention(Q_(s))were compared.Results The particle sizes and PDI of Rut-MS and Rut-NS were(1317.46±107.27,211.66±1.06)nm and 0.367±0.029,0.233±0.011,respectively.The Q_(24),J_(s),t_(lag),and Q_(s) of Rut-microgel and Rut-nanogel were(19.5482±4.769,31.8065±4.401)μg/cm^(2),(3.74±0.44,1.760±0.50)μg/cm^(2)·h,16.92,10.68 min,and(0.3661±0.2132,0.1692±0.0733)μg/cm^(2),respectively.The Q_(24) and J S of Rut-nanogel were 1.62 and 2.13 times higher than those of Rut-microgel,t_(lag) was 6.24 min shorter than Rut-microgel,and the Q_(s) of Rut-microgel is 2.16 times higher than that of Rut-nanogel.Conclusion The decrease of Rut particle size can promote the transdermal absorption rate of Rut-microgel,increase the amount of permeation,and shorten the tlag of permeation.