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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5362_Библиотеки_им_академика_М_И_Перельмана.pdf
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Graphene-Based Nanomaterials for Drug Delivery
An’amt Mohamed Noor, Farah Amanina Mohd Zin, Nasrun Hasenan,
and Lee Seong Wei
Abstract The rapid advancements in nanotechnology have paved the way for devel-
oping efficient and targeted drug delivery systems using nanomaterials. Among
various nanomaterials, graphene-based nanocomposites have shown great potential
for drug delivery applications owing to their unique physicochemical characteristics,
including a substantial surface area, exceptional mechanical strength, and high electrical conductivity. This chapter in book aims to provide a comprehensive overview
of the design, synthesis, and applications of graphene-based nanomaterials for drug
delivery. The content is divided into six sub-topics, which collectively cover the
essential aspects and recent advancements in the field.
Keywords Graphene
regeneration
· Drug delivery
· Graphene oxide · Synthesis methods · Neuronal
Abbreviations
AFM Atomic Force Microscopy
AIDS Acquired Immuno Deficiency Syndrome
Arg-Gly-Asp Arginylglycylaspartic
CH4 Methane
CrGO Chemically Reduced Graphene Oxide
Cu2O Cuprous Oxide
A. Mohamed Noor (B) · F. Amanina Mohd Zin
Advanced Materials Research Cluster, Faculty of Bioengineering and Technology, Universiti
Malaysia Kelantan, Jeli Campus, 17600 Jeli Kelantan, Malaysia
e-mail: anamt@umk.edu.my
N. Hasenan
Pathologi Department, Hospital Raja Perempuan Zainab ll, 15586 Kota Bharu, Kelantan, Malaysia
L. Seong Wei
Department of Agricultural Science, Faculty of Agro-Based Industry, Universiti Malaysia
Kelantan, Jeli Campus, 17600 Jeli Kelantan, Malaysia
229
230 A. Mohamed Noor et al.
CuO Cupric Oxide
CV Cyclic Voltammetry
CVD Chemical Vapor Deposition
DNA Deoxyribonucleic acid
Fe3O
4
Iron Oxide
GO Graphene Oxide
GNR Graphene Nanoribbons
GQDs Graphene Quantum Dots
H
2
Hydrogen
HGQD Hyaluronic Acid Graphene Quantum Dots
HN-1 TSPLNIHNGQKL
HOPG Highly Oriented Pyrolytic Graphite
HT-29 Human Colorectal Adenocarcinoma Cell Line
ITO Indium Tin Oxide
LSV Linear sweep voltammetry
MnO
2
Manganese Oxide
MPa Mega Pascal
N
2H4
NaBH
NaNO
4
3
Hydrazine
Sodium Borohydrate
Sodium Nitrate
NiO Nickel Oxide
NIR Near Infra Red
PCL Polycaprolactone
PDT Photodynamic Therapy
PEG Polyethyene Glycol
PET Polyethylene terephthalate
PTT Photothermal Therapy
rGO Reduced Graphene Oxide
RGQD Reduced Graphene Oxide Quantum Dots
RNA Ribonucleic Acid
SCENIHR Scientific Committee on Emerging and Newly Identified Health
Risks
SiC Silicon Carbide
SiO
2
Silicone Dioxide
siRNA Small Interfering Ribonucleic Acid
TiO
2
Titanium Dioxide
ZnO Zinc Oxide
ZrO
2
Zirconium Dioxide
Graphene-Based Nanomaterials for Drug Delivery 231
1 Introduction
Graphene, a remarkable two-dimensional material, has revolutionized the field of
nanoscience and nanotechnology since its discovery in 2004 by Andre Geim and
Konstantin Novoselov. Composed of a single layer of carbon atoms arranged in a
hexagonal lattice, graphene exhibits extraordinary properties such as light, claimed to
be the strongest material on earth, impermeable, highly conductive, and high surface
area that make it a subject of intense scientific interest and a promising candidate
for various applications. Graphene’s many characteristics is illustrated in Fig. 1.In
this chapter, we will delve into the fundamental properties of graphene and explore
different types of graphene derivatives, such as graphene oxide and reduced graphene
oxide for drug delivery.
Graphene possesses a remarkable combination of properties that make it an exceptional material for multiple applications. Firstly, it exhibits exceptional mechanical
strength, with a tensile strength over 100 times greater than steel [1]. This remark-
able strength, coupled with its flexibility and lightness, makes graphene an ideal
candidate for drug delivery s ystems, enabling the development of robust and flexible
nanocarriers. Secondly, graphene demonstrates outstanding electrical conductivity,
allowing it to efficiently carry electrical currents. This property is particularly relevant
in the design of electro-responsive drug delivery systems, where external stimuli can
trigger drug release [2]. By incorporating graphene into such systems, researchers
can exploit its electrical conductivity to achieve precise and controlled drug release
profiles. Furthermore, graphene exhibits excellent thermal conductivity, enabling
efficient heat dissipation in nanoscale devices. This property is crucial in the development of thermal-triggered drug delivery systems, where localized heating is used
Fig. 1 Properties of graphene
232 A. Mohamed Noor et al.
to release drugs at target sites. Graphene with high thermal conductivity properties
facilitates rapid and uniform heat distribution, enhancing the effectiveness of such
drug delivery strategies [3].
Graphene oxide (GO) is a derivative of graphene that has gained considerable
interest in the field of drug delivery application. GO is obtained by oxidizing
graphene, resulting in the introduction of oxygen-containing functional groups on its
surface. The oxidation procedure enhances the water solubility of GO, rendering it
extremely appropriate for the developmentof drug delivery systems based on aqueous
solutions. GO’s unique structure allows for facile functionalization and loading of
therapeutic molecules [4]. The oxygen functionalities on its surface provide reactive
sites for the attachment of targeting ligands, drugs, and imaging agents. This feature
enables the system design of multifunctional drug delivery capable of targeted drug
delivery and simultaneous imaging for real-time monitoring of therapeutic outcomes.
Besides that, reduced graphene oxide (rGO) is derived from GO through a reduction process that removes a significant portion of the oxygen functional groups. This
2
reduction leads to the restoration of sp
carbon–carbon bonds, enhancing the electrical conductivity and biocompatibility of rGO [5]. These properties make rGO a
promising candidate for drug delivery applications. The improved electrical conductivity of rGO facilitates the development of electro-responsive drug delivery systems.
By incorporating rGO into such systems, researchers can exploit its conductive nature
to achieve on-demand drug release through external stimuli, including electrical or
magnetic fields. This capability opens new avenues for personalized and site-specific
drug delivery. Moreover, rGO exhibits enhanced biocompatibility compared to pristine graphene. The reduction process eliminates many of the oxygen groups responsible for potential cytotoxicity, making rGO more suitable for biomedical applications. This biocompatibility, combined with its high drug-loading capacity, paves the
way for the development of safe and efficient drug delivery systems.
1.1 Challenges in Conventional Drug Delivery Systems
Conventional drug delivery methods have long faced challenges that limit their efficiency and effectiveness. This chapter delves into the limitations posed by conventional systems and explores the advancements made in targeted drug delivery, aiming
to overcome these hurdles and revolutionize the field of medicine.
1.1.1 Limited Drug Targeting: Unlocking Precision Medicine
Conventional drug delivery systems often lack the ability to specifically target the
affected site in the body. This non-specific distribution of drugs can lead to unwanted
side effects and decreased therapeutic efficacy. However, recent advancements have
paved the way for precision medicine and targeted drug delivery. Researchers have
developed innovative techniques such as nanotechnology-based carriers, liposomes,
Graphene-Based Nanomaterials for Drug Delivery 233
and monoclonal antibodies that can deliver drugs precisely to the affected tissues
or cells [6]. By utilizing these targeted approaches, drug delivery can be optimized,
maximizing therapeutic benefits while minimizing systemic side effects.
1.1.2 Overcoming Low Drug Solubility: Enhancing Bioavailability
The poor solubility of many drugs in water or biological fluids has long posed a challenge to conventional delivery systems. Limited solubility can impede drug absorption and bioavailability, compromising their effectiveness [7]. To address this issue,
scientists have explored various strategies. Nanoparticles and micelles are engineered
to encapsulate poorly soluble drugs, enhancing their solubility, and allowing for better
absorption. Additionally, prodrug approaches have been developed to convert poorly
soluble drugs into more soluble forms within the body,improving their bioavailability
and therapeutic potential.
1.1.3 Prolonging Drug Action: Sustained Release Systems
Rapid drug clearance and metabolism can significantly limit the therapeutic effect of
certain drugs. Conventional drug delivery systems may not provide sustained release
or protection against enzymatic degradation, resulting in a shorter duration of action
and the need for frequent dosing. To overcome this challenge, sustained release
systems have been developed. These systems incorporate specialized formulations,
such as biodegradable polymers or hydrogels, which can gradually release drugs over
an extended period. By achieving controlled and prolonged drug release, therapeutic
levels can be maintained, reducing the need for frequent dosing, and improving
patient compliance [8].
1.1.4 Enhancing Drug Stability: Innovative Formulations
Certain drugs are inherently unstable in their native form or prone to degradation
under specific conditions. Conventional drug delivery systems may not offer sufficient protection to maintain drug stability during storage and transport, potentially
compromising their efficacy. To address this issue, scientists have developed innovative formulations that enhance drug stability. Examples include lyophilization, which
involves freeze-drying drugs to increase their shelf life, and the use of protective
coatings or encapsulation techniques to shield drugs from environmental factors [9].
These advancements ensure that drugs retain their potency and efficacy throughout
the delivery process.
234 A. Mohamed Noor et al.
1.1.5 Patient-Friendly Approaches: Simplifying Treatment Regimens
Patient compliance is a critical factor in the success of any treatment. However, some
drug formulations require frequent dosing or complex administration procedures,
making it challenging for patients to adhere to the prescribed treatment regimen. To
improve patient compliance, researchers have focused on developing user-friendly
drug delivery systems. This includes the design of long-acting implants, transdermal
patches, and inhalation devices that offer convenient administration and reduce the
burden on patients [10]. By simplifying treatment regimens, these advancements aim
to enhance therapeutic outcomes and overall patient satisfaction.
1.2 Overview of Nanomaterials for Drug Delivery
Drug development and delivery techniques have undergone a remarkable change
over the past few decades and are still evolving today as they go from the traditional
micro-scale to the cutting-edge nanoscale. The bold objective of extending human life
expectancy t hrough the advancement of drug delivery systems serves as the driving
force behind this paradigm shift. Precision medicine now has a world of possibilities
thanks to scientists and researchers who have embraced the potential of nanotechnology. These nanoscale drug carriers and delivery platforms increase therapeutic
efficacy while minimizing side effects, offering up new treatment options for diseases
that were previously incurable. They do this by precisely targeting particular cells,
tissues, or organs within the body. Nanotechnology integration has enormous potential to improve healthcare and enhance patient outcomes on a global scale. Figure 2
demonstrates the harm caused to healthy organs or cells when conventional drugs
were supplied without the use of nanocarriers. Contrarily, contemporary techniques
use nanomedicines to deliver pharmaceuticals to certain locations within the body,
hence nanomaterial offers more enhanced possibility to improve healthcare system.
1.3 Role of Graphene-Based Nanomaterials in Drug Delivery
Graphene-based nanomaterials offer unique characteristics such as high surface area
(2630 m
(Young’s modulus) with benchmark values of 42 N m
versatile functionalization capabilities. This chapter explores the role of graphenebased nanomaterials in revolutionizing drug delivery systems, enabling precise and
efficient therapeutic interventions.
for enhancing drug loading and encapsulation. By functionalizing graphene with
specific moieties, it becomes capable of interacting with various drugs, enabling
efficient loading and controlled release. The surface functionalization also allows
2
g−1), superior mechanical strength including breaking and tensile strength
−1
and 1.0 T Pa [12], and
Graphene’s large surface area and unique structure make it an excellent candidate