Preparation Of Photothermal Responsive Microspheres Integrated Microneedles Fro Drug Deliveryapplication

Stratagems of drug delivery are one of great significance for disease treatment and other biomedical fields.Hydrogel microspheres(MPs)are effective for drug delivery owning to softness,high specific surface area and good biocompatibility.In particular,intelligent responsive hydrogels could release drugs immediately and controllably through sensitive reactions stimulated by external microenvironment.However,the traditional MPs delivery strategy may lead to wound,pain and even skin infection,which greatly complicates the application process.At present,microneedle(MN)array has attracted much attention because of its ability to penetrate the skin without pain,overcome the stratum corneum barrier and create microchannels to enhance drug delivery,which is a promising strategy for transdermal drug delivery.In addition,the regulation of MNs material and structure can also realize instantaneous and long-term drugs administration.Integrating the responsive hydrogel MPs into the painless and portable MNs avoids the risk of drug inactivation and skin infection,and achieves painless,portable and versatile drug delivery.Based on the photothermal responsive hydrogel MPs and soild MNs,we developed the integration of intelligent MPs and MNs system,and constructed two kinds of multi-function,painless portable drug delivery devices.These devices could be used to encapsulate different types drug and evaluate its multi-channel subcutaneous delivery effect.Specific work include the following:(1)Preparation and characterization of photothermal shrinkage hydrogel MPs-MNs:MPs containing near infrared response black phosphorus and temperature shrinkable Nisopropylacrylamide were prepared by a capillary microfluidic device.Then,the MPs were filled into the MN array by template replication method.The morphology of MPs and composite MPs-MNs were characterized by microscopy,the photothermal response ability of responsive MPs was optimized,and the mechanical strength of the composite MPs-MNs system was explored.(2)Preparation and characterization of separable photothermal phase-changing hydrogel MPs-MNs:MPs consisted of near infrared response to black phosphorus and temperature phase-changing gelatin were prepared by microfluidics.The particle size and responsiveness of MPs were optimized.After that,MPs were filled into microneedles,and their morphology was characterized by microscope after demoulding.Then,we explored the regulation of near-infrared trigger on the phase transition of MPs and further regulation on the separation of microneedles.Finally,the effect of MPs on the mechanical strength of MNs was explored.(3)Drug delivery of photothermal responsive hydrogel MPs-MNs:drug loading and release ability of the above two MPs-MNs systems were investigated.Fluorescent molecules with similar molecular weight were applied to replace drugs and wrapped in corresponding MPs and MNs,and their loading capacity to drug molecules was analyzed.The release effect of drugs from the above two microsphere microneedle systems was evaluated qualitatively and quantitatively by fluorescence.Such composite systems had the satisfactory biocompatibility.