Porous And O₂ Propellant-loaded Polymer Microneedles For Fast Transdermal Extraction And Delivery

Microneedles（MNs）with micron-sized 3D array structures can penetrate the skin stratum corneum barrier and deliver drugs directly into the skin with the advantages of painlessness and easy operation.In particular,polymer MNs have been widely used in the fields of skin interstitial fluid extraction,disease diagnosis,and treatment due to their good biocompatibility and easy processing properties.Among these polymer MNs,porous MNs and dissolving MNs are frequently used for their rapid interstitial fluid extraction and drug delivery.However,the poor hydrophilicity of existing porous polymer MNs makes it difficult to achieve rapid liquid extraction/drug delivery.On the other hand,the dissolving and diffusion of dissolving MNs in the skin tissues are limited by the entanglement of polymer chains.Aiming at solving these problems,this dissertation presents a phase inversion method to prepare porous polymer MNs with interconnected pores and introduces oxygen propellant into dissolving polymer MNs,realizing rapid extraction of skin interstitial fluid and drug delivery for transdermal theranostics.The main contents of this dissertation are as follows:（1）A phase inversion method was developed to prepare porous polymer MNs with interconnected pores,which can be further extended to the preparation of porous MNs with commonly used biomedical polymers,such as cellulose acetate,polylactic acid,polyethersulfone,and so on.Taking porous cellulose acetate MN as an example,the porosity of the MN can be well controlled in 40%（v/v）～90%（v/v）by regulating the concentration of the polymer solution,and the resultant MNs could penetrate mice skin and extract interstitial fluid effectively in vivo.In addition,we showed that there was almost no difference between the glucose concentration in the skin interstitial fluid extracted by the porous MNs and the blood glucose concentration in the tail vein of mice detected by glucometer.（2）Hydrophilic and anti-adhesion polymer MNs were obtained by coating the polydopamine and poly（ethylene glycol）on the surface of polymer MNs via a bioinspired method.By introducing the-NH₂ or-OH group,the contact angle of water on the porous MNs surface was decreased to<41°.Therefore,they can achieve rapid extraction in vitro.The anti-protein adhesion level of the polymer surface was increased by 60%,and the superficial adhesion amount of molecules with different weights and charges was less than10%after being modified with poly（ethylene glycol）.（3）Carbon nanotubes（CNT）were incorporated into the porous polymer MNs.By blending carbon nanotubes in polymers,the modulus of composite CNT MNs can be increased from 43 MPa to 97 MPa.In addition,the introduction of CNT endowed the composite CNT MNs with good photothermal performance.The surface temperature of the MNs can quickly rise to 50.2℃after being irradiated with an 808 nm laser.Moreover,the composite MNs loaded with the chemotherapeutic drug（doxorubicin）can deliver the drug to the subcutaneous tumor,exhibiting a combined therapeutic effect of photothermal and chemotherapy in breast tumor-bearing mice.（4）Dissolving polymer MNs loaded with“oxygen propellent”from sodium percarbonate were developed.When the MNs were inserted into the skin of the mice,the sodium percarbonate can be released after the MN matrix dissolving,which reacted with water to generate oxygen and form convection in the liquid,accelerating the migration speed of the photosensitizer-loaded in MNs both in the F-127 gel and the skin.The rapid migration of photosensitizers and the production of oxygen effectively improved the level of reactive oxygen species in hypoxic breast cancer cells,increasing the cell-killing effect from 29.2%to 99.0%.Therefore,the“oxygen propellent”-loaded MNs exhibited a good anti-tumor effect in a tumor-bearing mouse model.