It has been extensively accepted that carbon-based materials including graphene, carbon nanotubes and fullerene are playing important roles in advanced science and technology as well as practical application. These advanced carbon-based materials have been and will continue to be incorporated in various applications such as sensing, high-performance composites, molecular electronics, field emission devices, biomedical application, environmental protection.
As one of the most widely used categories of carbon nano materials, graphene is 2-dimensional single sheet of carbon atoms arranged in a hexagonal network with interesting physical and electronic properties (Wang X et al., 2016; Miraftab et al., 2017). Graphene can exist in different forms; whereas the most important ones are graphene nano sheets, graphene oxide (GO), reduced graphene oxide and graphene oxide quantum dots. It has been well documented for the research related to applying graphene and graphene-family nano materials in the fields like biosensing, energy‐related devices, biomedical, etc. However, the challenge still remains, particular for those associated with medical or drug delivery applications. In this commentary, we focused on several successful examples of graphene-based materials that have been integrated with other green-based materials and utilized for drug delivery systems. Graphene has been explored in drug delivery systems due to the presence of aromatic rings, free electrons, vacant reactive sites at the edges of graphene structure. Such an unique structure allows graphene to accommodate different drugs (i.e., water- insoluble aromatic drugs or water-soluble ones) via covalent and non-covalent dynamic bonding interaction, e.g., hydrogen bonding, hydrophobic interaction, π-π interactions and electrostatic interactions. Moreover, graphene-based materials have shown excellent biocompatibility, low toxicity, prominent thermal and mechanical stability, which provide potential prospects for the development of drug carrier substances. The shortcoming of graphene implementing in drug delivery system is its low solubility in aqueous solution. However, the aqueous stability and solubility of graphene could be improved by inducing π-π interactions with aromatic drug molecules or other organic molecules.
On the other hand, GO, a chemically modified graphene, is an attractive precursor to be solved by simple mixing with other materials because of oxygen-containing group (epoxides, alcohols, and carboxylic acids groups) at the basal plane as well as at the edges of graphene oxide. Consequently, it can be stably dispersed in aqueous solutions as well as physiological environments. One noticeable characteristic about GO-based drug delivery systems is attributed to its two accessible sides for drug binding; and these vacant sites tend to contribute significantly to the increasing of drug loading amount (Ghawanmeh et al., 2019).
Recently, a considerable amount of work has been focused on the combination of graphene and its derivatives with other molecules or materials to extend and enhance applications of the GO based materials. Among a variety of organic materials, cellulose and cellulose-derived materials have emerged as a novel class of promising bio-based materials used in drug delivery. Compared with other nano drug carrier, cellulose materials have many advantages including renewability, non-toxicity and biodegradability. Moreover, the porous structures of cellulose and its derivatives (gel-like cellulose in particular) facilitate the liquid uptake of the cellulose as absorbent materials; and meanwhile, enable them to act as an appropriate drug excipient or drug carrier. Whether the combination of graphene and cellulose could lead to hybrid materials or nanocomposites as drug carrier has attracted enormous research interests. The potential of such hybrid materials for drug delivery has been explored recently. For instance, Wang R et al. (2017) synthesized pH-sensitive hybrid aerogel based on carboxymethyl cellulose (CMC) and GO, which relied on the advantage of pH responsive behavior of the CMC for the controlled release of drug triggered by pH. The Ca+2 was used as an effective crosslinker for the incorporation or intercalation of the CMC into the GO sheets to minimize the electrostatic repulsion between GO and CMC. The results showed that the delivery of anticancer drug from the hybrid aerogel of CMC/GO/chitosan is promising and pH-sensitive.
In another work, a novel nanocomposite hydrogel was prepared based on carboxymethyl cellulose, graphene quantum dot for loading and releasing naproxen as a nonsteroidal anti-inflammatory drug. The copper acetate was implemented as an ionic crosslinker for the CMC to produce spherical beads (Javanbakht et al., 2018). Different from most other types of physical crosslinkers suitable for CMC, copper acetate renders the pH of solution close to neutral or so acidic, thus benefiting pH-sensitive drugs. Similar approach was also reported by Rasoulzadeh et al. (2017) for synthesizing CMC-GO nanocomposite hydrogel beads with the aid of FeCl3·6H2O as a physical crosslinker which associates the carboxyl groups on CMC via simple coordination with metal ion (Fe+3), leading to the crosslinked hybrid hydrogel. The resulting CMC/GO hydrogel nanocomposites crosslinked in such a manner turn to be very sensitive to pH. The complete release of drugs was achieved in the acidic media.
Rao et al. (2018) functionalized and modified GO with adipic acid dihydrazide (ADH) to generate GO-CMC hybrid gel via amide linkage. The amino groups at the terminal of GO-ADH react with the carboxyl groups of CMC through the well-known crosslinking system NHS/EDC (i.e., N-hydroxy sulfosuccinimide and 1-ethyl- (dimethylaminopropyl) carbodiimide) to induce the chemical crosslinking. In the next step, antitumor drug was loaded onto the surface of the conjugate by π-π stacking (via GO) and hydrogen bonding interactions and its drug loading and in vitro release were studied. Authors claimed that the anticancer drugs could reach the vicinity of cancer cells for targeted therapy due to the pH responsivity.
To conclude, the graphene/cellulose hybrid hydrogel or aerogel addressed above appears to be promising and feasible for application, although there is strong demand on modifying these hybrid nanocomposites to have better functionality and multi-responsive behaviors (such as thermo- and redox responsive) for drug carrier systems. The scope of these articles above was just focused on the CMC as hydrogel matrix. The work should be extended to nanofibrillated cellulose (NFC) as the building blocks of hybrid composite. The integration of other types of cellulose in conjunction with graphene should be considered in drug delivery system. On the other hand, graphene nanosheets tend to aggregate in solution, mainly driven by the enhanced van der Waals attractive forces between graphene sheets, which raises technical difficulties during the fabrication of graphene-based drug delivery systems. It is still challenging to have fully dispersed graphene in cellulose matrix. The approaches developed in the past in the exfoliation of nanoclay for nanocomposites might be adaptable in the current hybrid systems consisting of graphene and various types of cellulose.
Feasibility and Potential of Graphene and Its Hybrids with Cellulose as Drug Carriers:A Commentary
- Received Date: 2019-09-21
- Available Online: 2019-10-01