Microfluidic Approach for Enhanced Paeoniflorin Transdermal Delivery: A Comparative Study on Different Chips and Mixing Dynamics

Paeoniflorin is a natural pharmaceutical ingredient with a widely biological activity. However, as a hydrophilic drug, the problem of low transdermal rate limits its clinical application. To overcome this shortage, LUVs were used as biocompatible carriers of paeoniflorin in this study. We prepared paeoniflorin-loaded large unilamellar vesicles (LUVs) with W/O/W structure by microfluidics. We used four kinds of chips to prepare paeoniflorin LUVs and explored the effects of the chip structures on LUVs properties applying both experiments and numerical simulations. The difference of fluid mixing mechanisms was analyzed among four different channels, including straight and curved structures. Then we evaluated the differences in skin permeability among the three groups, paeoniflorin aqueous solution group, drug-loaded liposome group and blank liposome & drug mixture group, using the abdominal skin of male mice. The results showed that the structure of the microfluidic channel was a key factor affecting the flow rate and mixing efficiency. The mixing efficiency further affected the liposome size. The mixing efficiency of curved channel was not better than that of a straight channel due to the low flow rate and long mixing time. By the results of transdermal experiments, LUVs could reduce the transdermal time and increase the total transdermal amount. LUVs effectively improved the transdermal absorption efficiency of paeoniflorin. In conclusion, paeoniflorin LUVs with highly efficient transdermal were successfully prepared by using microfluidics. We explored the underlying fluid dynamics that lead to variations in the preparation with different chip structures. The transdermal effect of the LUVs was verified.