Paeoniflorin, the main component of total glucosides of paeony (TGP), shows good therapeutic effects in arthritis, but has low bioavailability when administered orally. Avoiding such a deficiency for topical administration would expand its clinical application. This study aimed to avoid these limitations by using nanotechnology (ethosomes) and a physical approach (microneedles). Paeoniflorin-loaded ethosomal formulation (TGP-E) was optimized and evaluated in terms of entrapment efficiency (EE), particle size (PS), zeta potential (ZP), polydispersity index (PDI) and morphology. TGP-E was prepared by the hot injection method and optimized by single-factor tests and an orthogonal experimental design. The optimized paeoniflorin-loaded ethosomes had EE of 27.82 ± 1.56%, PS of 137.9 ± 7.57 nm with PDI of 0.120 ± 0.005, ZP of −0.74 ± 0.43 mV. Ethosomes showed a nearly spherical shape under the transmission electron microscope (TEM). The optimal microneedle-assisted (MN-assisted) conditions were obtained at a microneedle length of 500 μm, a pressure of 3 N and an action time of 3 min. The cumulative penetration amounts (Qn) of TGP solution transdermal (ST) and MN-assisted TGP solution transdermal (MST) were 24.42 ± 8.35 μg/cm2 and 548.11 ± 10.49 μg/cm2, respectively. Qn of TGP-E transdermal (PT) and MN-assisted TGP-E transdermal (MPT) were 54.97 ± 4.72 μg/cm2 and 307.17 ± 26.36 μg/cm2, respectively. These findings indicate that use of ethosomes and microneedles can both enhance the penetration ofpaeoniflorin, but for the water-soluble drug, there is no obvious synergism between nanotechnology and microneedles for enhancing penetration in a transdermal drug delivery system.

Cui et al.: Ginsenoside Rg3-loaded PEGylated liposomesIn this study, ginsenoside Rg3-loaded PEGylated liposomes were prepared and optimized using the Box-Behnken design. These liposomes were characterized, the cumulative release profiles were investigated and compared with ginsenoside Rg 3 -loaded liposomes in vitro. To improve the stability ginsenoside Rg3-loaded PEGylated liposomes were freeze-dried and the lyoprotectants to be added were screened. The results showed that the liposomes have a small particle size (152.58±0.74 nm) and spherical shape. The encapsulation efficiency and drug-loading rate were approximately 85.24±1.02 and 7.44±0.08 %, respectively. For lyoprotectants, 2 % lactose was chosen as the lyophilized protectant according to the appearance, re-dispersity, particle size, and entrapment efficiency of lyophilization of ginsenoside Rg3loaded PEGylated liposomes. In vitro release showed that ginsenoside Rg3-loaded PEGylated liposomes showed a more obvious sustained release effect, which suggests that ginsenoside Rg3-loaded PEGylated liposomes might enhance the therapeutic effect of ginsenoside Rg3.

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To establish a method for detecting micro-dialysis recovery of paeonol, eugenol and piperine in Huoxue Zhitong patch, in order to provide the basis for further percutaneous pharmacokinetics studies. The concentrations of paeonol, eugenol and piperine in dialysates were determined by HPLC, and probe deliveries were calculated respectively. The effects of concentration and calibration approaches on the micro-dialysis probe deliveries of the three components were investigated, and their probe absorbability, in vitro and in vivo probe stability and repeatability were also studied.The results indicated that little paeonol, eugenol and piperine were observed in probes with 30% alcohol as the perfusate, and could be cleaned from probe in a short time. And the in vivo and in vitro probe deliveries of three components were stable within 8 h, drug-containing solution and blank perfusate were alternatively used for three times, and the in vivo and in vitro probe deliveries of three components were basically unchanged. The in vitro recoveries of paeonol, eugenol and piperine with a range of concentration were respectively (45.7±4.66)%, (27.82±2.95)%, (41.3±3.96)%, which indicated no concentration independent. Under the same conditions, the similar delivery was observed by dialysis, retrodialysis and no-net flux. Therefore, the concentrations of analyses of the collected fraction could be calibrated by in vitro or in vivo recoveries. Meanwhile, this also proved that the micro-dialysis method built by this study is applicable to the study on percutaneous pharmacokinetics of Huoxue Zhitong patch.

Purpose: To study the in vitro penetration and in vivo pharmacokinetics of ferulic acid (FA), and the correlation between them after dermal administration. Methods: Franz diffusion cell was used to study in vitro penetration of FA. The concentration of FA in the Franz receiver solution was assessed by high performance liquid chromatography (HPLC). Prior to in vivo pharmacokinetics experiments, probe recovery was validated with respect to influencing factors such as flow rate, FA concentration, within-day stability and reproducibility of the probes. In in vivo pharmacokinetic experiment, six male CD-1 hairless mice were used. The micro-dialysis (MD) probe was implanted in the dermis of the rat skin, and dialysates from probe outlet were quantified directly by HPLC. In in vivo studies, deconvolution methods were used to determine the relationship between in vitro and in vivo data, and the correlation coefficient of linear equations. Results: There was significant effect of pH (5 ~ 8) on the penetration of FA. Increase in pH caused commensurate decrease in permeability. The Cmax of FA was 300.74 ± 31.86 ng/mL while Tmax was 138.00 ± 22.80 min after dermal administration of 1 mg/mL FA dissolved in phosphate buffered saline (PBS). The correlation coefficient (r) between in vitro and in vivo data was 0.9905. Conclusion: Both in vivo and in vitro experiments demonstrate that FA permeates the stratum corneum of skin rapidly. The unionized form of FA shows better penetration than the ionic form. In addition, results from correlation analysis indicate that the in vitro penetration characteristics of FA can be applied to predict its in vivo pharmacokinetics.