| Microneedles are micron-sized needles commonly used in needle arrays placed on a substrate to form microneedle patches.Due to their convenient transdermal action,they have been widely used in the fields of transdermal drug delivery,tissue fluid extraction and detection,and medical cosmetology.Microneedle transdermal administration can avoid drug loss caused by digestive system metabolism,often seen in traditional oral and needle injections.It also provides a painless puncture,which improves patient compliance,has simple operation,and is low cost.However,the interaction between the microneedle and skin is complex during the insertion process of the microneedle patch.The change of geometric parameters of the microneedle patch will affect the insertion performance,which in turn affects the microneedle patch’s transdermal drug delivery effect.Moreover,the existing microneedle patch delivery rate is slow,which can cause skin irritation and damage.This paper designed and prepared separable microneedles.The model,simulation,and experiment of the microneedle insertion process were used to explore the influence of different geometric parameters on microneedle insertion performance.Furthermore,PLGA/nHAp hydrogel and effervescent gel were modulated to prepare rapidly separable degraded microneedles,and their insertion performance was studied.This study has guiding significance for microneedle patch size selection,design,and the preparation of microneedles for separable sustained-release drug delivery.First,using different instant equations,a three-dimensional simulation model of microneedle patch piercing was established based on the mechanical properties of multilayer soft tissues and the mechanical properties of PLGA/nHAp hydrogels.By conducting soft tissue tensile and compression experiments with skin layer and fat layer,the obtained experimental results were fitted to obtain the applicable intrinsic constitutive equations.The mechanical properties of PLGA/nHAp hydrogel and the coefficient of friction between PLGA/nHAp hydrogel and skin layer were measured.A geometric model was established based on the microneedle patch dimensions,using different instant equations,a three-dimensional simulation model of microneedle patch piercing was established based on the mechanical properties of multilayer soft tissues and the mechanical properties of PLGA/nHAp hydrogelsto set the boundary conditions between microneedles and soft tissues,the friction coefficient and mutual contact.An in vitro piercing experimental platform was built,and suitable experimental samples and microneedle patches were selected for validation experiments.The accuracy of the simulation model was verified by comparing and analyzing the simulation and experimental results under the same parameters.Secondly,modeling,simulation and experiments were conducted for different geometric parameters of the microneedle penetration process,and the influence of different geometric parameters on microneedle penetration performance was investigated.A mechanical model with different tilt angles and plane numbers was established to qualitatively investigate the trend of piercing force changes due to parameter variations.The penetration process of microneedles with different parameters was simulated by the simulation model,and the penetration force and soft tissue deformation of skin were investigated.Selected microneedle patches with some parameters were prepared,and the penetration force,penetration rate and penetration depth were validated and analyzed using an in vitro penetration platform.The results of modeling,simulation and experiments showed that appropriately increasing the gap,aspect ratio and number of planes would improve the penetration performance of microneedles to a certain extent.Then,PLGA/nHAp hydrogels and effervescent gels with good mechanical properties were modulated.The harmless and slowly degradable PLGA/nHAp hydrogels were formulated and the mechanical properties of the hydrogels were studied at different ratios of PLGA/nHAp.The mechanical properties of PLGA/nHAp hydrogels were studied at different ratios of PLGA/nHAp.The fast disintegrating effervescent gels were formulated by changing the percentage of disintegrant and binder.The disintegration rate and mechanical properties of the effervescent gels were analyzed experimentally,and the disintegration rate of the gels accelerated and the mechanical properties decreased with the increase of the disintegrant ratio.The PLGA/nHAp hydrogel with a PLGA/nHAp ratio of 1:1 and the effervescent gel with a disintegrant/binder ratio of 1:1 is selected.Finally,detachable microneedle patches were designed and prepared.In this paper,we designed the step-by-step preparation of separable microneedles by assemblable molds and prepared separable microneedles by step pouring PLGA/nHAp hydrogel and effervescent gel into the molds using PLGA/nHAp hydrogel and effervescent gel.The mechanical properties,separation rate,and drug tip retention rate of the separable microneedles were investigated by experiments.The detachable microneedles have a higher drug delivery rate than conventional microneedles,are less irritating to the skin,and can avoid the damage caused by tip breakage,making them more valuable for practical applications. |
