Fabrication Of A NIR-responsive Microneedle Patch For Nitric Oxide Delivery And Application In Ischemic Perforator Flaps

Objective: Skin necrosis is the most serious complication of the flap plastic surgery,which means the failure of the operation.Systemic administration rarely benefits the local and has hidden bleeding risks,while topical administration has poor permeability due to the skin barrier function.Currently,few of these methods can totally respond to the blood supply of the skin after surgery.Therefore,there is an urgent need for a safe,simple,painless,and precise topical administration for ischemic skin treatment.Methods: The soluble microneedle(MN)patch was used to target the ischemic area in a painless and precise manner for transdermal drug delivery.Based on the important role of nitric oxide(NO)in angiogenesis,the thermosensitive NO donor(BNN6)and gold nanorods(GNRs)acting as photothermal agents were introduced into the microneedle(MN)patch to attain the GNRs-BNN-MN patch.The hyperthermia induced by GNRs under near infrared(NIR,808 nm)irradiation could facilitate the NO release from BNN6 to promote angiogenesis.Results: The MN patch made of hyaluronic acid had the ability to penetrate the epidermis and the drug was released as the MN patch dissolved.Under the NIR(808nm)irradiation,the GNRs-BNN-MN patch heated up steadily to accelerate the penetration of drugs and release NO from BNN6.Cell experiment results showed that the GNRs-BNN-MN patch had good biocompatibility and promoted the proliferation and migration of human umbilical vein endothelial cells(HUVECs)under the NIR(808 nm)irradiation.Finally,the GNRs-BNN-MN patch with NIR(808 nm)irradiation was used to treat ischemic perforator flaps on rat’s back and it achieved ideal results.The survival rate of the flaps was improved.From histological examination,it was found that the microvessel density and the expression of VEGF protein of flaps increased.Conclusion: We developed a NIR-responsive soluble microneedle patch for heating up and NO delivery.This system provided a simple,safe,precise and effective treatment method for the ischemic perforator flaps.