Design And Preparation Of Degradable Microneedle For Transdermal Delivery Of Drugs

Diabetes mellitus,as one of the oldest diseases,has been a concern for a long time in the world.Effective treatments have been improving since the early part of the 20 th century.Although great progress has been achieved in recent decades,daily insulin injections still disrupt the diabetic patient’s daily life.Recently,the microneedles(MNs)drug delivery system has received intense investigation because it offers a painless and minimally invasive approach to pierce the outermost skin layer,the stratum corneum,with its microscopic needles.Among them,the MNs made from dissolving or biodegradable polymers are of great promise.Because they can be completely and safely dissolved or degraded within the skin to release the loaded drugs in the meanwhile.In this thesis,different polymers were used to fabricate degradable microneedles for application on diabetic rats.Furthermore,a controllable microneedles transdermal drug delivery system triggered by near-infared light(NIR)was developed.The drug release properties and transdermal delivery on diabetic rats were investigated.The thesis contains three parts as follows:1.The calcium sulfate and gelatin biodegradable composite microneedle patches with high aspect-ratio microneedles(MNs)and a flexible substrate have been developed.The microneedles exhibit excellent mechanical property which can achieve 0.4 N for each needle.Insulin,the drug to control blood glucose levels in diabetic patients,has been embedded into the biodegradable composite MNs.The hypoglycemic effect for transdermal delivery of insulin is studied using diabetic SpragueDawley(SD)rats as models in vivo.After transdermal administration to the diabetic rats,the released insulin from biodegradable composite MNs exhibit an obvious and effective hypoglycemic effect for longer time compared with that of subcutaneous injection route.This work suggests that biodegradable composite MNs containing of insulin have a potential application in diabetes treatment via transdermal ingestion.2.The polymer microneedle patches that fabricated from modified alginate and hyaluronate were prepared for transdermal delivery of insulin.The as-prepared microneedles(MNs)exhibited excellent mechanical strength to penetrate the skin and good degradability to release loaded insulin.In vitro skin insertion capability was determined by application of rhodanmine B loaded microneedle on skin tissue,and the penetration depth was observed by histological sections.Confocal microscopy images revealed that the rhodamine B and fluorescein isothiocyanate-labeled insulin(FITCinsulin)can gradually diffuse from the puncture sites to deeper tissue.In vivo studies were then conducted to estimate the feasibility of the administration of insulin-loaded microneedle patches on diabetic mice for glucose regulation.The results suggests the MNs developed in this study have a promising application in diabetes treatment via transdermal delivery.3.Near-infrared light triggered and separable microneedles(MNs)have been fabricated by separately molding method.The photothermal conversion agent(Prussian blue nanoparticles,PB NPs)and hypoglycemic drug(metformin)have been embedded into the separable polycaprolactone(PCL)MNs arrowheads.The as-fabricated MNs exhibited an excellent photothermal conversion properties under near-infrared light(NIR)irradiation,causing the MNs arrowheads to melt due to the photothermal conversion of PB NPs.After applied on skin,the separable MNs arrowheads could be embedded in the skin due to the dissolving of supporting substrate after absorbing the interstitial fluid.When the embedded MNs arrowheads were exposed to NIR irradiation,the MNs arrowheads undergone a rapid thermal ablation from a solid to a liquid state,which allowed on-demand control of timing and dose of drug released.It suggests the developed NIR-triggered and separable MNs are a promising transdermal drug delivery system that enables the patient or physician to adjust therapy precisely in an active manner,thus,improving treatment efficiency and reducing side-effects.