Photothermal Activatable Mucoadhesive Fiber Mats for On-Demand Delivery of Insulin via Buccal and Corneal Mucosa

Electrospun fiber mats loaded with therapeutics have gained considerable attention as a versatile tool in the biomedical field. While these bandages are largely based on fast-dissolving polymers to release the cargo, stimuli-responsive fiber mats have the advantages of providing a timely and spatially controlled drug delivery platform, which can be refilled and reused several times. These benefits make electrospun fiber patches original platforms for painless and convenient on-demand hormone release. Because of the high need of more convenient and non-invasive methods for delivering insulin, a hormone that is currently used to treat hundred million people with diabetes worldwide, we have investigated the tremendous potential of reduced graphene oxide modified poly(acrylic acid) based fiber mats as an original platform for buccal and corneal insulin delivery on-demand. The PAA@rGO hydrogel-like fibers rendered water-insoluble by incorporating β-cyclodextrin, followed by thermal cross-linking, which showed adequate tensile strength along with high adsorption capacity of insulin at pH 7 and good recyclability. The fiber mats maintained good fibrous morphology and high loading efficiency even after five loading-release cycles. The mucoadhesive nature of the fibers allowed their application for insulin delivery via the eye cornea and the buccal mouth lining, as evidenced in ex vivo studies. Insulin loaded PAA@rGO hydrogel-like fibers showed an insulin flux via buccal lining of pigs of 16.6 ± 2.9 μg cm-2 h-1 and 24.3 ± 3.1 μg cm-2 h-1 for porcine cornea. Testing on healthy adult volunteers confirmed the excellent, mucoadhesive nature of the bandage, with three out of six volunteers feeling completely comfortable (note 8.3) while wearing the patches in the buccal cavity.The Centre National de la Recherche Scientifique (CNRS), the University of Lille, the Hauts-de-France region, and the CPER “Photonics for Society” are acknowledged for financial support. This work was partly supported by the French Renatech network. A.V. thanks the i-SITE foundation of the University of Lille for a PhD fellowship. This project has received funding from the European Union’s Horizon 2020 Research and Innovation Staff Exchange (RISE) Marie Skłodowska-Curie Actions under grant agreement No 690836.Peer reviewe