GBH - 'GRAPHENE-BASED HYDROGELS' OR GRIEVOUS BODILY HARM?

Considering events over the last few years, the reason for re-posting the below article is clear.

The main question remains simple.

Have graphene-based hydrogels been used in the C19 vaccination programme?

The secondary questions are less simple:

Are the jabbed public now suffering high levels of graphene oxide making them more susceptible to EMFs and radiation?
Are the hydrogels malfunctioning and causing blood clots?

The below 'copy and pasted' taster-article is for a key study (hiding behind a copyright wall) from Science Direct. We are republishing the taster-article as the information is of importance for the public's information and well-being.

Beyond traditional hydrogels: The emergence of graphene oxide-based hydrogels in drug delivery

Abstract

Hydrogel applications in various medical fields especially in drug delivery have been widely investigated in the last few years. Introduction of biopolymers in the production of hydrogels leads to develop biodegradable, biocompatible, and non-immunogenic drug carriers. However, possessing such remarkable properties the role of hydrogels is still limited in drug delivery because of the factors such as insufficient loading capacity particularly for hydrophobic drugs, poor mechanical strength, low homogeneity, and inadequate response to stimuli. Hence to address such shortcomings the two-dimensional (2-D) carbon-based nanomaterial, graphene holding various significant properties has been introduced to this three-dimensional (3-D) structure for their more prominent performance in drug delivery. This 2-D and 3-D combination made researchers to develop required features to the already existed traditional polymer hydrogels. Graphene and its derivatives exploited the practical applications of conventional hydrogels by acting as gelator to self-assembled graphene-based hydrogels (GBH) as well as a filler to blend with small and macromolecules to produce multifunctional GBH. Herein the progress with GBH in various field focusing their role in drug delivery as a nanocarrier has been empathetically revealed. Amid the limitations and factors affecting the performance of graphene and hydrogels along with their properties and methods of preparations have also summarized. Further, the development and challenges of GBH have correspondingly prospected.

Introduction

Nanomedicine is defined as a branch of medicines based on nanotechnology - that deals with the development and manipulation of materials at 1–100 nm for the diagnoses, prevention, monitoring, imaging, treatment of diseases and also to regenerate the biological system [1,2]. Nanomedicine proved a great potential for therapies of several disease states and presented many ground-breaking discoveries in past. Recent advances in nanomedicine brought an evolution in pharmaceutical and medicinal fields and became well esteemed at the commercial level around the world [3,4]. Over the last few decades, US FDA has approved about 100 nano-medicines which shows immense role of nanotechnology in medical field [5]. Several studies revealed that the strategies based on nanotechnology for drug delivery led to better absorption and biodistribution of drug in a controlled manner with fewer side effects along with precise targeting [6]. The basic properties of systems used for delivery of drugs which can be tailored at nanoscale level through monitoring controlling factor have been shown in Fig. 1.

There are several traditional routes for delivery of drugs such as oral, trans-dermal, intra-nasal, intra--venous, intramuscular, subcutaneous, pulmonary, buccal & rectal [7]. After administering into the body the drug has to face various types of biological barriers such as immune system, biological hydrogels such as mucus, epithelial cell barrier and bloodstream to act at the site of action [8,9]. These conventional strategies for transporting the drug to site of action have several types of limitations such as instability, toxic, narrow range therapeutic range, and solubility problems [10]. To address the short comings of conventional approaches various nanomaterial incorporated drug delivery systems have been successfully designed. The current findings in this direction illustrate some promising ways in which nanomaterials as drug carriers can assist in navigating the biological barriers [11]. Their smaller size, greater area of surface and capability to interface to cells/tissues are remarkable features which are responsible for their demand in biomedical applications [[12], [13], [14]].

In general, nanoparticles are the structures having size range between 1 and 100 nm and over past few decayed they are playing marvelous roles at the frontiers of nanomedicine covering drug delivery, tissue engineering, microfluidics, biosensors, etc. [15,16]. Among these liposomes and micelles were 1st generation of systems having nanoparticles which got FDA approval. These systems are capable of holding NPs (inorganic nanoparticles) such as nano-particles of gold/magnetic and results in increasing utilization of inorganic nanomaterials for several therapeutic purposes [15,17]. Both organic and inorganic nanomaterials played a vital role in various fields and in case of medicinal application, organic NPs are considered suitable agents as they offer great biodegradability and biocompatibility characteristics, but in comparison to inorganic NPs they show lesser stability in the environment [6,18].

During recent decades, drug delivery formulations are designed by using natural biopolymers as raw materials due to their desirable and exclusive properties like non-toxicity, environmental sensitivity, renewability, bio-compatibility, and biodegradability. Chitosan, sodium alginate, starch, guar gum, and konjac glucomannan are examples of biopolymers but these biopolymers are associated with several shortcomings like delicate mechanical properties and free release of drugs. In this way, by using natural biopolymer as drug carriers, the adverse effects of drug therapy are rare to avoid. These drawbacks are basically due to the poor bonding between drugs and biopolymers or due to rapid breakdown of biopolymer carriers throughout the drug release process [19]. Additionally, sustained release profile of drugs can be achieved by using biodegradable polymers and encapsulating drug within polymer, but sometimes due to availability of the limited number of binding fictional sites, drugs are not capable to attach through the polymer. Thus, it is needed to improve further drug therapeutic action. Hence to evade such difficulty, the requirement of developing or discovering more efficient drug carriers is needed [20]. Various attempts have been made by numerous researchers to discover new carrier structure for targeting and for achieving expected control drug release profile including various organic and inorganic nanoparticles using proniosomes, silica nanoparticles, magnetic nanoparticles, alginate beads, hydrophilic colloids, hydrogels, effervescent floating tablet, microspheres and lipid solid dispersion, transdermal patches etc. [[21], [22], [23], [24], [25], [26], [27], [28]]. Several nanomaterials categorized as organic and inorganic used as drug carrier are shown in Fig. 2 and a brief description of the same is given in Table 1.

Nowadays, the preparation of composite of novel nanomaterial/biopolymer as controlled drug delivery vehicles have become more popular due to their extraordinary structure and properties since it was known that the properties of biopolymer vehicles can be improved by using methods like mixing with other polymers and grafting with monomers [19,20]. Till to date various nanocomposites exploiting graphene & its derivatives have been designed by researchers having wide spectrum of uses. These nanocomposites of graphene are broadly categorized into two types i.e., first are those nanocomposites which are formed due encapsulation of nanoparticles (NPs) within graphene; and second, are those which creates nanoparticles (NPs) and are decorated over the graphene sheet. A variety of derivatives of graphene viz. graphene oxide (GO) along with reduced graphene oxide (rGO) for growth of various sorts of NPs [29,30] have been used for formation of nano-composites.

Hydrogel possessing tremendous advantages are still adhere with some major limitations, so to address such shortcomings this (graphene) carbon-based nanomaterial has been introduced by the researchers. Through this review we aimed to provide an up-to date overview of the research on graphene derivative based hydrogel, to cover a diverse range of perspective or emerging trends in this direction. The studies which could impart significantly impact on further research with robust outcomings have been taken into account.

Section snippets

Bio-medical applications of graphene-based nanomaterial

The characteristic of a novel carrier includes biocompatibility, drug binding sites, nontoxic nature, safer elimination, excellent drug solubility and specificity for site [19]. The current innovation of GO has gained great consideration of the researchers in current years, owing to its potentiality of providing most of the above mentioned individuality as a carrier for delivery of drugs [49].

GO, possesses a honeycomb 2D crystal lattice having a solo coating of sp2-hybridized carbon atoms. Due

Biocompatibility and toxicity of graphene oxide

GO has been widely employed for many different biomedical purposes; however, there has been discussion over its toxicity and biocompatibility, and an exact conclusion has not yet been found. Moreover, the dosage, functionalization, synthesis process, and experimental design seem to have a significant impact on its toxicity and biocompatibility [67,68]. Lu et al. reported that the lipid bilayer of Escherichia coli is physically disrupted by GO nanosheets. In a similar manner depending on the

Graphene oxide as a nanocarrier

The properties required to become an ideal carrier for drug release were shown by GO, in comparison with them and thus it can be a possible option to the existing drug carriers for their organized release. The novel functional monohybrids can be designed by chemical modification of graphene that could play an essential purpose in delivery of drugs and may be valid in many other biomedical fields too, for example, tissue engineering and biosensing, cancer therapies, imaging, etc. [76].

Goenka et

Hydrogels

Treatment with traditional drugs involves repeated dosing of a drug that has been formulated in a manner to ensure its stability, bioavailability, and activity. The conventional methods for formulation of majority of therapeutic agents are relatively efficient but have some problems like instability, toxic, narrow therapeutic range, and show excessive solubility problems. Hence, need firm compliance or usage for a long time. In these cases, to retain predetermined plasma drug levels usually, a

Graphene oxide-based hydrogels drug delivery system

In recent years, graphene-based materials have been researched for use in tissue engineering, regenerative medicine, wound healing, and stem cell engineering. Since it has superior mechanical qualities high elasticity, strength, and flexibility graphene can be tailored to perform a variety of functions on flat surfaces. As a result, it could be put to use as a reinforcing component in hydrogels, biodegradable films, electrospun fibres, and other tissue engineering scaffolds [353,354].

Many newer

Properties that can be improved by incorporating GO hydrogels

Integrating graphene oxide (GO) into hydrogels has great potential for improving certain essential characteristics. Significantly, the incorporation of GO may greatly enhance the mechanical robustness of hydrogels, thereby overcoming a key drawback observed in conventional hydrogel materials. The addition of this reinforcement enhances the overall strength and longevity of the hydrogel, broadening its potential uses in diverse areas such as tissue engineering and drug delivery. Moreover, the

Methods of preparation of graphene-based hydrogels

The basic approaches for the making of graphene-based hydrogels are self-assembly, mixed solution and in-situ polymerization methods which are discussed as follows in brief [364].

Applications of hydrogels based on graphene oxide for the administration of drugs

It has been established that GO holding various oxygen-containing functional groups, make it a viable option as a vehicle for the desirable delivery of pharmaceuticals or DNA. In spite of the presence of functional groups, they exhibit remarkable loading capacity, great solubility, and outstanding biocompatibility as a result of their high surface area and basal planar structure with a sp2 domain. It is feasible to build multimodal GO with a range of functions through the process of conjugating

Conclusion

Since last few decayed, in the direction of drug delivery, researchers are focusing to generate novel drug carriers for control and targeted delivery by using amazing properties of nanomaterials. The review investigated the applications of graphene oxide, and due to its distinct physicochemical characteristics, it is able to couple with both hydrophilic and hydrophobic molecules either covalently or non-covalently, has been declared as a significant nano-vector for drug deliver amid its

Credit authorship contribution statement

Renu Saharan: Conceptualization, Data curation. Sarvesh K. Paliwal: Data curation, Formal analysis. Abhishek Tiwari: Formal analysis, Investigation. M. Arockia Babu: Investigation, Methodology. Varsha Tiwari: Formal analysis. Randhir Singh: Software, Supervision. Suresh Kumar Beniwal: Visualization, Writing – review & editing. Manish Kumar: Investigation, Methodology. Ajay Sharma: Investigation, Software. Waleed Hassan Almalki: Validation, Visualization. Imran Kazmi: Supervision, Validation.