Near-infrared light activatable hydrogels for metformin delivery

Abstract

Drug loaded hydrogels have proven to be versatile controlled-release systems. We report here on heat active hydrogels' formation by mixing graphene oxide (GO) or carboxyl enriched reduced graphene oxide (rGO-COOH) with metformin hydrochloride, an insulin sensitizer drug currently used as 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 Human hepatocyte model confirmed that metformin activity was unaffected by photothermal activation.In vivo, metformin was detected in mice plasma at 1h post-activation of the metformin loaded rGO-COOH gel.

Developing an analytical method by HPLC for simultaneous quantification of methylene blue and metformin applied to in vitro skin permeation and retention studies

“…The amount of drugs permeated through the skin was below the LOQ, for both formulations, which is interesting, because the systems minimize possible adverse effects resulting from the systemic absorption of the drugs, particularly the MET that has shown transdermal absorption for some systems (Chengnan et al, 2019;Migdadi et al, 2018;Rostamkalaei, Akbari, Saeedi, Morteza-Semnani, & Nokhodchi, 2019;Yu et al, 2018Yu et al, , 2019. F I G U R E 2 Delivery of MB and MET in the different layers of the skin (SC and VE + D) after 12 h of exposure to the formulations: 0.25% poloxamer dispersion (P) or 0.25% poloxamer dispersion containing 10% (w/w) ethanol (P + EtOH).…”

“…Although there are different methods for quantifying MB and MET in their isolated form or associated with other substances (Chengalva, Angala Parameswari, & Aruna, 2016;Chengnan et al, 2019;Chhetri, Thapa, & Van Schepdael, 2014;Khdair, Handa, Mao, & Panyam, 2009;Prasanna & Priyanka, 2015;Rengelshausen et al, 2004;Rostamkalaei, Akbari, Saeedi, Morteza-Semnani, & Nokhodchi, 2019;Umapathi, Ayyappan, & Darlin Quine, 2012;Wang et al, 2009), few studies quantify these substances in a matrix as complex as the skin (Chen et al, 2020;Garcia et al, 2018;Junqueira et al, 2016;Polonini et al, 2019;Yu et al, 2018Yu et al, , 2019 and some of them employ quantitative methods that are not selective (Garcia et al, 2018;Junqueira et al, 2016) or standardized for other matrices such as plasma and urine, which may not be suitable for quantification in the different layers of the skin (Yu et al, 2018(Yu et al, , 2019; moreover, there are no studies in the literature that quantify the two substances simultaneously and in the different layers of the skin (SC and viable epidermis + dermis, VE + D).…”

Wound Healing: From Passive to Smart Dressings

“…[ 76 ] While many current smart wound dressings are capable of measuring one or two wound parameters, the next generation of smart wound dressing can simultaneously monitor essential chemical and physical parameters involved in the wound healing, including pH, moisture, temperature, and uric acid (UA), in a single flexible device. [ 77–79 ]…”

Hydrogel design strategies for drug delivery

“…The gelation process is attributed to hydrogen bonds and electrostatic interactions between GO and metformin. The photothermal activation of GO induces the dissolution of the gels through irradiation with NIR light, triggering the sustained release of metformin (60). Another example of a particulate gel where sustained release can be triggered by ultra-sound was achieved with 10 nm magnetite nanoparticles (115).…”