Transdermal skin patch based on reduced graphene oxide: A new approach for photothermal triggered permeation of ondansetron across porcine skin

Abstract

The development of a skin-mounted patch capable of controlled transcutaneous delivery of therapeutics through thermal activation provides a unique solution for the controlled release of active principles over long-term periods. Here, we report on a flexible transdermal patch for photothermal triggered release of ondansetron (ODS), a commonly used drug for the treatment of chemotherapy-induced nausea and vomiting and used as model compound here. To achieve this, a dispersion of ODS-loaded reduced graphene oxide (rGO-ODS) nanosheets were deposited onto Kapton to produce a flexible polyimide-based patch. It is demonstrated that ODS loaded Kapton/rGO patches have a high drug delivery performance upon irradiation with a continuous laser beam at 980nm for 10min due to an induced photothermal heating effect. The ability of ODS impregnated Kapton/rGO patches as transdermal delivery scaffolds for ODS across the skin is in addition investigated using porcine ear skin as a model. We show that the cumulative quantity and flux of ODS passing the skin are highly depending on the laser power density used. At 5Wcm irradiation, the ODS flux across pig skin was determined to be 1.6μgcmh comparable to other approaches. The use of tween 20 as skin enhancer could significantly increase the ODS flux to 13.2μgcmh. While the skin penetration enhancement is comparable to that obtained using other well-known permeation enhancers, the actual superiority and interest of the proposed approach is that the Kapton/rGO photoactivatable skin patch can be loaded with any drugs and therapeutics of interest, making the approach extremely versatile. The on demand delivery of drugs upon local laser irradiation and the possibility to reload the interface with the drug makes this new drug administration route very appealing.

On demand electrochemical release of drugs from porous reduced graphene oxide modified flexible electrodes

“…It is also in contrast to the recently reported photothermal release of ODS on photothermally activatable skin patches: 24 irradiation for 30 min resulted in a release of 15% ODS, while electrochemical release of ODS after 30 min was between 5 and 7%. However, while the photothermal approach resulted in a release maximum after 30 min irradiation, the release of ODS as shown here is constant over a long period of time.…”

“…Such a flux is highly promising for follow up transdermal studies where ODS fluxes between 1 μg cm −2 h −1 and 4 μg cm −2 h −1 are reported. 24,25,34 Considering that the usual oral dose of ODS is between 16 and 32 mg a day and the oral bioavailability of ODS is 60%, for an effective ODS delivery system, about 10-20 mg a day should be delivered into the blood circulation, i.e. 2.5-5 mg every 6 h. 35 A K/Au-prGO/ODS electrode of 1 cm 2 delivers about 282 μg ODS in 6 h. An electrode of around 10 cm 2 in size is theoretically needed to deliver the daily amount required.…”

“…19 Even though ODS is validated as a good candidate for patients receiving highly emetogenic agents, its use has been limited in people having difficulties in swallowing after chemotherapy. Besides oral delivery, numerous alternative delivery systems have been investigated, including transdermal [20][21][22][23][24] and nasal administration. 25 We have recently developed a flexible transdermal patch for the photothermal triggered release of ODS.…”

“…We have demonstrated that these ODS loaded patches have a high drug delivery performance upon irradiation with a continuous laser beam at 980 nm due to an induced photothermal heating effect. 24 The other drug investigated is the antibiotic AMP, as treatment of bacterial infections is still one of the most challenging tasks in the biomedical field. With the overuse of antibiotics and the resulting growing number of multidrug-resistant bacteria, the development of on demand antibiotic delivery systems is a practical strategy for reducing the generation of antibiotic resistance and increasing the lifespan of newly developed antibiotics.…”

Functionalization of Reduced Graphene Oxide via Thiol–Maleimide “Click” Chemistry: Facile Fabrication of Targeted Drug Delivery Vehicles

“…Reduced graphene oxide (rGO) nanosheets with restored sp 2 network have most lately shown to be ideally suited for drug-loading-and drug-release-based applications using electrical (1)(2)(3) as well as thermal induced triggers. (4)(5)(6)(7)(8)(9)(10) Although the majority of the aromatic scaffold of rGO is devoid of any functional groups, a few carboxylic acid and alcohol groups are present at the edges and other defect points. This limits the effective functionalization of the rGO through covalent transformations.…”