Design And Preparation Of Drug-Loaded Microtexture Of Microneedle Array For Dermatological Treatment

Skin is the largest organ of the human body.Dermatosis is a general term for diseases occurring in the skin and its accessory organs.Skin diseases not only affect physical and mental health,but also cause panic and social discrimination,so more and more scientific attention.At present,the main external treatment of skin diseases is drug coating on the skin surface.This method has a low drug absorption rate,and increasing drug dosage will lead to the risk of secondary infection such as allergy,which is an urgent problem to be solved in the current medical field.In this paper,to meet the technical requirements,we designed a microne array with drug-carrying micro-texture structure,and combined with focused ion beam processing technology(FIB)for microne level processing,to prepare a microtexture microne array with complete structure,and improve the delivery efficiency and absorption rate of transdermal drugs.In this paper,the minimum of Young’s modulus of each crystal direction of monocrystalline silicon was set as the material of microneedle array,and a variety of microneedle array,such as triangular pyramid,quadrilateral pyramid,pentalateral pyramid and conical pyramid,were designed respectively.The Ogden hyperelastic model in ANSYS was selected to replace the actual skin,and the statics module and the display dynamics module were used to construct the microneedle array to completely puncture multi-layer skin model.The needle shape and size of the microneedle array were analyzed,and the optimal microneedle shape was determined to be a 4-pyramid,with a length of 200 μm,a width of 160 μm,and a spacing distance of 420 μm.The round,rectangular and oval microtextures of drug loading were further designed.The results show that the rectangle texture is the smallest texture shape with the same drug loading.Numerical verification of the micro-texture of the microneedle array puncture skin shows that the texture has high strength without fracture.Using Stopping and Range of Ions in Matter(SRIM)to simulate microtexture processing of gallium(Ga)ion sputtering,the sputtering yield,range,energy analysis and material damage of monocrystalline silicon materials were studied.Using the "Detailed Calculation with full Damage Cascade" simulation method,the analysis shows that 30 keV is the most suitable Ion energy for processing,and the sputtering yield is 2.19Atoms/Ion under this condition.The maximum energy absorbed by the silicon material is 112.80 eV,the Ion range is 279 A,and the energy loss of recoil phonon is the highest(53.23%).The total number of vacant Atoms is 810 Atoms/Ion.The micro-texture was processed on a microneedle array using FIB technology.High-precision processing with dual-beam FIB equipment was carried out to remove the tip of the microneedles with a length of 6.25μm and form a plane of about 25μm2,thus reducing the probability of the damaged tip remaining in the skin.The same micro-texture grooves were processed on the two sides of the micro-scale.Incident ions sputtered monocralline silicon targets at angles of 30° and 45° on the inclined horizontal plane,and three micro-texture grooves of equal width and spacing were processed from top to bottom.The lowest micro-texture parameter was the largest,with a length of 66μm,a width of 20μm,and a depth of 120μm.The grooves produced by FIB sputtering are smooth and have complete micro-texture and sufficient space to accommodate drug solution.The experiment verified the feasibility of microtexture microneedle array for drug delivery through skin puncture.Viscosity and contact Angle tests were performed for three classes of drugs used to treat dermatosis to assess drug storage in microtextured grooves.The cell proliferation state of microneedle array in contact with mouse epidermal cells was detected by cytotoxicity test.It was found that the 24-hour cell survival rate of microneedle array and control group was similar and extremely high.The survival rate of microneedle array group reached 99.42%,which proved that the microneedle array had good biocompatibility.KM mice with young age and no hair growth were selected to puncture the skin with drugs carried by micro-texture microneedles array,and the drug retention in the skin was observed.The experimental results showed that the drug coverage area of micro-texture microneedles exceeded that of ordinary microneedles by 70.52%～105.09%,and the drug amount of residual skin of micro-texture microneedles with 30° horizontal Angle was greater than that of micro-texture microneedles with 45°horizontal Angle.The high drug loading of micro-texture microneedle array was confirmed.