Electrothermal patches driving the transdermal delivery of insulin.

Transdermal patches have become a widely used approach for painless delivery of drugs. One major current limitation of these systems remains the restricted skin permeation of proteins and peptides as exemplified by insulin, necessitating different considerations for their successful transdermal delivery. We present a novel patch design based on the integration of nano-engineered heating elements on polyimide substrates for electrothermal transdermal therapy. The results reveal that tuning of the electrical resistivity of an array of gold nanoholes, patterned on polyimide, facilitates a fast-responding electrothermal skin patch, while post-coating with reduced graphene oxide offers capabilities for drug encapsulation, like insulin. Application of insulin-loaded patches to the skin of mice resulted in blood glucose regulation within minutes. While demonstrated for insulin, the skin patches might be well adapted to other low and high molecular weight therapeutic drugs, enabling on-demand electrothermal transdermal delivery.

Near-infrared light activatable hydrogels for metformin delivery.

Drug loaded hydrogels have proven to be versatile controlled-release systems. We report here on heat active hydrogel formation by mixing graphene oxide (GO) or carboxyl enriched reduced graphene oxide (rGO-COOH) with metformin hydrochloride, an insulin sensitizer drug currently used as the first line therapy to treat patients with type 2 diabetes. The driving forces of the gelation process between the graphene-based nanomaterial and metformin are hydrogen bonding and electrostatic interactions, weakened at elevated temperature. Using the excellent photothermal properties of the graphene matrixes, we demonstrate that these supramolecular drug reservoirs can be photothermally activated for transdermal metformin delivery. A sustained delivery of metformin was achieved using a laser power of 1 W cm-2. In vitro assessment of the key target Glucose-6 Phosphatase (G6P) gene expression using a human hepatocyte model confirmed that metformin activity was unaffected by photothermal activation. In vivo, metformin was detected in mice plasma at 1 h post-activation of the metformin loaded rGO-COOH gel.

Particle-based photodynamic therapy based on indocyanine green modified plasmonic nanostructures for inactivation of a Crohn's disease-associated Escherichia coli strain.

Particle-based photodynamic therapy (PPDT) holds great promise in theranostic applications. Herein, we demonstrate that PPDT based on gold nanorods coated with an indocyanine green (ICG)-loaded silica shell allows for the inactivation of the Crohn's disease-associated adherent-invasive Escherichia coli strain LF82 (E. coli LF82) under pulsed laser light irradiation at 810 nm. Fine-tuning of the plasmonic structures together with maximizing the photosensitizer loading onto the nanostructures allowed optimizing the singlet oxygen generation capability and the PPDT efficiency. Using a nanoparticle concentration low enough to suppress photothermal heating effects, 6 log10 reduction in E. coli LF82 viability could be achieved using gold nanostructures displaying a plasmonic band at 900 nm. An additional modality of nanoparticle-based photoinactivation of E. coli is partly observed, with 3 log10 reduction of bacterial viability using Au NRs@SiO2 without ICG, due to the two-photon induced formation of reactive oxygen species. Interaction of the particles with the bacterial surface, responsible for the disruption of the bacterial integrity, together with the generation of moderate quantities of singlet oxygen could account for this behavior.