Effect Of Star Silicon Microneedles On Transdermal Delivery Of Adenosine

Objective:This study aims to investigate the effects of silicon microneedle(MN)pretreatment on skin permeability and pharmacodynamics of adenosine.Methods:Scanning electron microscopy(SEM)was employed to characterize the apparent array structure of the MN.The skin surface morphology after the microneedles pretreatment on the skin were observed under optical microscope.An analysis method of adenosine was established and validated using high performance liquid chromatography(HPLC).Adenosine-loaded oil in water emulsion(Ad-O/W)was prepared by emulsification and evaluated,such as morphology,pH value,dispersion uniformity and stability.Skin irritation test was conducted to investigate the preliminary safety of MN application on rat skin.The effects of microneedle pretreatment on the penetration of adenosine through rat skin were investigated in Franz diffusion cells.After that,a subacute skin aging model based on D-galactose injection and UV irradiation was constructed to investigate the effects of Ad-O/W and MN treatment.The skin moisture,elasticity,wrinkle volume and apparent skin morphology were observed in detail.Hematoxylin-Eosin staining(H&E)was used to characterize the skin tissue after various treatment.Dmetrix software was used to determine the thickness of the epidermis and dermis of ICR mice.Results:SEM images showed that the silicon MN arrays were homogeneously distributed and each needle displayed pyramid shape.MN treatment could effectively puncture the stratum comeum.The analysis method showed a good linear relationship between adenosine concentration and HPLC peak area with precision and accuracy meeting the methodological requirements.The uniform particle size of Ad-O/W was observed under optical microscope.The pH value and drug concentration of Ad-O/W were 6.72±0.09 and 10 mg.g-1,with satisfied physical stability.The results of irritation test showed that when the retention time of MN on the skin was shorter than 2 min,there was no visible irritation.In vitro permeation test indicated that adenosine solution was difficult to penetrate rat skin,while Ad-O/W had showed certain permeability through rat skin.Interestingly,MN pretreatment on the skin could significantly improve the skin permeability of adenosine in rats.The accumulated skin permeability for 8 h and permeation rate of Ad-O/W were 33.86±1.64 ?g.cm-2 and 4.23 ?g.cm-2.h-1,respectively,which were about 4.49-times and 3.13-times of those in the untreated group.The combination of Ad-O/W and MN could notably improve the hydration and elasticity of aging skin,reduce the wrinkles,improve the skin morphology,reduce the atrophy of epidermal and dermal thickness caused by skin aging.Also,the thickness of epidermis and dermis were increased,which shows good anti-skin aging effect.Conclusion:Microneedle pretreatment could significantly increase the skin permeability of adenosine in O/W emulsion without obvious skin irritation.This study might provide a beneficial information for the further research of microneedles in the transdermal delivery of hydrophilic drugs.