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Tailoring drug release rates in hydrogel-based therapeutic delivery applications using graphene oxide.

ABSTRACT: Graphene oxide (GO) is increasingly used for controlling mass diffusion in hydrogel-based drug delivery applications. On the macro-scale, the density of GO in the hydrogel is a critical parameter for modulating drug release. Here, we investigate the diffusion of a peptide drug through a network of GO membranes and GO-embedded hydrogels, modelled as porous matrices resembling both laminated and 'house of cards' structures. Our experiments use a therapeutic peptide and show a tunable nonlinear dependence of the peptide concentration upon time. We establish models using numerical simulations with a diffusion equation accounting for the photo-thermal degradation of fluorophores and an effective percolation model to simulate the experimental data. The modelling yields an interpretation of the control of drug diffusion through GO membranes, which is extended to the diffusion of the peptide in GO-embedded agarose hydrogels. Varying the density of micron-sized GO flakes allows for fine control of the drug diffusion. We further show that both GO density and size influence the drug release rate. The ability to tune the density of hydrogel-like GO membranes to control drug release rates has exciting implications to offer guidelines for tailoring drug release rates in hydrogel-based therapeutic delivery applications.

SUBMITTER: Puvirajesinghe TM

PROVIDER: S-EPMC5832740 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Tailoring drug release rates in hydrogel-based therapeutic delivery applications using graphene oxide.

Puvirajesinghe T M TM Zhi Z L ZL Craster R V RV Guenneau S S

Journal of the Royal Society, Interface 20180201 139

Graphene oxide (GO) is increasingly used for controlling mass diffusion in hydrogel-based drug delivery applications. On the macro-scale, the density of GO in the hydrogel is a critical parameter for modulating drug release. Here, we investigate the diffusion of a peptide drug through a network of GO membranes and GO-embedded hydrogels, modelled as porous matrices resembling both laminated and 'house of cards' structures. Our experiments use a therapeutic peptide and show a tunable nonlinear dep ...[more]

PMID: 29445040

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Project description:Intratumoral (IT) injection of chemotherapeutics into needle-accessible solid tumors can directly localize the anticancer drug in the tumor site, thus increasing its local bioavailability and reducing its undesirable effects compared to systemic administration. In this study, graphene oxide (GO)-based chitosan/β-glycerophosphate (CS/GP) thermosensitive injectable composite hydrogels (CH) were prepared and optimized for the localized controlled delivery of doxorubicin (DOX). A quality-by-design (QbD) approach was used to study the individual and combined effects of several formulation variables to produce optimal DOX-loaded GO/CS/GP CH with predetermined characteristics, including gelation time, injectability, porosity, and swelling capacity. The surface morphology of the optimal formulation (DOX/opt CH), chemical interaction between its ingredients and in vitro release of DOX in comparison to GO-free CS/GP CH were investigated. Cell viability and cellular uptake after treatment with DOX/opt CH were studied on MCF 7, MDB-MB-231 and FaDu cell lines. The statistical analysis of the measured responses revealed significant effects of the concentration of GO, the concentration of CS, and the CS:GP ratio on the physicochemical characteristics of the prepared GO/CS/GP CH. The optimization process showed that DOX-loaded GO/CS/GP CH prepared using 0.1% GO and 1.7% CS at a CS: GO ratio of 3:1 (v/v) had the highest desirability value. DOX/opt CH showed a porous microstructure and chemical compatibility between its ingredients. The incorporation of GO resulted in an increase in the ability of the CH matrices to control DOX release in vitro. Finally, cellular characterization showed a time-dependent increase in cytotoxicity and cellular uptake of DOX after treatment with DOX/opt CH. The proposed DOX/opt CH might be considered a promising injectable platform to control the release and increase the local bioavailability of chemotherapeutics in the treatment of solid tumors.

Project description:The novel controlled and localized delivery of drug molecules to target tissues using an external electric stimulus makes electro-responsive drug delivery systems both feasible and desirable, as well as entailing a reduction in the side effects. Novel micro-scaffold matrices were designed based on poly(lactic acid) (PLA) and graphene oxide (GO) via electrospinning. Quercetin (Q), a natural flavonoid, was loaded into the fiber matrices in order to investigate the potential as a model drug for wound dressing applications. The physico-chemical properties, electrical triggering capacity, antimicrobial assay and biocompatibility were also investigated. The newly fabricated PLA/GO/Q scaffolds showed uniform and smooth surface morphologies, without any beads, and with diameters ranging from 1107 nm (10%PLA/0.1GO/Q) to 1243 nm (10%PLA). The in vitro release tests of Q from the scaffolds showed that Q can be released much faster (up to 8640 times) when an appropriate electric field is applied compared to traditional drug-release approaches. For instance, 10 s of electric stimulation is enough to ensure the full delivery of the loaded Q from the 10%PLA/1%GO/Q microfiber scaffold at both 10 Hz and at 50 Hz. The antimicrobial tests showed the inhibition of bacterial film growth. Certainly, these materials could be loaded with more potent agents for anti-cancer, anti-infection, and anti-osteoporotic therapies. The L929 fibroblast cells cultured on these scaffolds were distributed homogeneously on the scaffolds, and the highest viability value of 82.3% was obtained for the 10%PLA/0.5%GO/Q microfiber scaffold. Moreover, the addition of Q in the PLA/GO matrix stimulated the production of IL-6 at 24 h, which could be linked to an acute inflammatory response in the exposed fibroblast cells, as a potential effect of wound healing. As a general conclusion, these results demonstrate the possibility of developing graphene oxide-based supports for the electrically triggered delivery of biological active agents, with the delivery rate being externally controlled in order to ensure personalized release.

Dataset Information

Tailoring drug release rates in hydrogel-based therapeutic delivery applications using graphene oxide.

Publications

Tailoring drug release rates in hydrogel-based therapeutic delivery applications using graphene oxide.

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