4.7 Article

Multilayered Microneedles for Triphasic Controlled Delivery of Small Molecules and Proteins

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MACROMOLECULAR BIOSCIENCE
卷 -, 期 -, 页码 -

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WILEY-V C H VERLAG GMBH
DOI: 10.1002/mabi.202300431

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antibody; drug delivery; microneedles; timed release

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In this study, a three-layer microneedle for controlled release of three different molecules is designed. The microneedles, efficiently generated through micromolding, have good mechanical integrity and effectively penetrate the skin. The three layers in the microneedles release the cargo in a three-phase manner.
Transdermal delivery is an attractive delivery method that increases bioavailability, is suitable for a wide variety of therapeutics, and offers stable delivery outcomes. However, many therapeutics are unable to readily cross the stratum corneum. Microneedles mechanically disrupt the cutaneous barrier to deliver small molecules, proteins, and vaccines. To date, microneedles have not been used in conjunction with coacervate, a liquid-liquid phase separation that protects unstable proteins. A three-layer microneedle for the controlled release of three different molecules is designed. Through micromolding, microneedles are efficiently generated, which benefits product scalability. The microneedles have good mechanical integrity and effectively penetrate porcine skin ex vivo. The three layers, in the microneedles, release the cargo in a three-phase manner. The released protein maintains its structure well. Moreover, layer thickness can be controlled by varying fabrication parameters. The microneedles can incorporate both small molecule drugs and protein therapeutics, thus promising uses in multi-drug therapies through a single treatment. Multilayered microneedles provide a basis for the sequential controlled delivery of multiple therapeutics including proteins, and small molecules. In this study the fabrication of these multilayered microneedles, their mechanical properties, release profiles of individual layers, and activity of the therapeutics are explored. There is great promise for future therapies from these microneedles.image

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