Objective To prepare transdermal peptide-modified osthole liposomes (TD-Ost-Lips), and to explore the transdermal permeation performance and its therapeutic effects on atopic dermatitis (AD). Methods TD-Ost-Lips were prepared by film dispersion method. Phospholipid to osthole amount ratio, phospholipid to cholesterol amount ratio and phospholipid to DSPE-mPEG₂₀₀₀-TD amount ratio were selected as main influencing factors, overall desirability (OD) of entrapment efficiency, drug loading and particle size acted as response values, and the Box-Behnken design-response surface method (BBD-RSM) was used to optimize preparations of TD-Ost-Lips. Shape of TD-Ost-Lips was observed by transmission electron microscopy (TEM). TD-Ost-Lips gel was prepared using carbomer 940 as matrix, drug release behavior in vitro was studied by dialysis method and the mechanism of drug delivery was also studied. The rheology of TD-Ost-Lips gel was explored. The Franz diffusion cell method was used to study the transdermal permeation performance of TD-Ost-Lips gels. Atopic dermatitis (AD) model was stablished, the changes of skin lesions on the back of the mice were observed, and the inflammatory factors and pathological changes of skin lesions were detected. Results The optimal formulations of TD-Ost-Lips: phospholipid to osthole amount ratio was 8.81:1, phospholipid to cholesterol amount ratio was 6.27:1 and phospholipid to DSPE-mPEG2000-TD amount ratio was 6.27:1. The encapsulation efficiency, drug loading, particle size and ζ potential of TD-Ost-Lips were (86.77 ± 0.71)%, (6.65 ± 0.10)%, (220.25 ± 5.69) nm, and (−17.31 ± 0.85) mV, respectively. The shape of TD-Ost-Lips were vesicular. The cumulative release rate of TD-Ost-Lips gel in 24 h was 77.06%, and the drug behavior accorded with Weibull model. The rheological properties of TD-Ost-Lips gels showed solid elastic properties, and did not flow when inverted. TD-Ost-Lips gel increased the permeation rate, cumulative penetration and skin retention of osthole to 5.00, 5.04 and 2.84 times, respectively. TD-Ost-Lips gel significantly reduced the psoriasis area and severity index (PASI), effectively suppressed the elevation of inflammatory factors in skin tissue, and enhanced the treatment effect of osthole on AD. Conclusion TD-Ost-Lips gel greatly promoted the transdermal permeation of osthole, significantly enhanced its therapeutic effects on atopic dermatitis, and laid a foundation for further development and application.

osthole  /  transdermal peptide  /  liposomes  /  gel  /  Box-Behnken design-response surface method  /  permeation rate  /  skin retention  /  atopic dermatitis