Gold Nanoparticles:A Boon To Drug Delivery System: December 2015

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Gold Nanoparticles:A Boon to Drug Delivery System

Article · December 2015


DOI: 10.22205/sijbs/2015/v1/i3/100407

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South Indian Journal of Biological Sciences 2015; 1(3); 127-133 Online ISSN:2454-4787

Gold nanoparticles: a boon to drug delivery system


Kashif Hussain1, Touseef Hussain 2,*
Gyani Inder Singh Institute of Professional Studies, Dehradun, Dehradun, Uttarakhand 248003, India
1

Deptartment of Life Science, Uttarakh and Technical University, Dehradun, Uttarakhand 248003, India
2

*Corresponding authors:
Touseef Hussain
E-mail: [email protected]

Manuscript details Abstract

Article History: Gold nanoparticles (AuNPs) are currently playing a significant role for human
Received 9 October 2015 welfare in the field of clinical diagnosis as well as several biomedical applications.
Revised 22 November 2015 More and more research shows that AuNPs-based technologies are becoming
Accepted 8 December 2015 promising approaches in diabetes, cancer research, chemotherapy, AIDS treat-
Published 28 December 2015 mentetc.AuNPs can be easily synthesized, functionalized, and are biocompatible.
The tenability of theAuNP monolayer allows for complete control of surface prop-
erties for targeting and stability/release using these nanocarriers.Nanoplatforms
Keywords: have been developed to manufacture of nanomedicines in preclinical and clinical
Gold nanoparticles studies for the administration of small molecules, genes, and peptides with im-
AuNPs provement of given in vivo behaviour. Similarly, NPs emerge as the future of drug
Nano carriers delivery technology as they might be future crucial diagnostic and therapeutic
Gene delivery tools. Of these, gold nanoparticles with their unique chemical and physical prop-
erties have emerge as promising carrier for delivery of various molecules with
therapeutic properties.This review will discuss several delivery strategies utilizing
AuNPs.

1. Introduction cells, stability over high temperatures and transloca-


tion into the cells, etc.. They also exhibit exceptional
Nanotechnology has provided research-level break- optical properties making them capable of producing
through in various industrial applications. Among quantum effects suitable for imaging applications.
those it has attained remarkable levels in medicine Most commonly studied metal nanoparticles include
(bio diagnostics, drug delivery and cancer therapy) gold, silver, titanium oxide and iron nanoparticles
(Ferrari 2005; Rosi and Markin 2005). These achieve- (El-Ansary and Al-Daihan 2009).
ments came from the usage of versatile nanomateri-
als.Nanomaterials are materials with the sizes in the 2. Drug delivery
range of 1 to several 100’s of nanometers, attracts an
ample attention in different fields of physics, chem- Drug delivery is the method or process of adminis-
istry, material science, medicine and biology, due to tering a pharmaceutical compound to achieve a ther-
their unique electronic, magnetic, optical, mechan- apeutic effect in humans or animals. Drug delivery
ical, physical and chemical properties. The char- technologies are patent protected formulation tech-
acteristic properties of nanoparticles are their (a) nologies that modify drug release profile, absorption,
small size (1–100 nm), (b) large surface-to-volume distributionand elimination for the benefit of improv-
ratio, (c) physical and chemical properties that can ing product efficacyand safety, as well as patient con-
be tuned depending upon the requirements of size, venience and compliance. Current efforts in the area
composition, and shape, (d) quantitative and qualita- of drug delivery include the development of targeted
tive target-binding properties and (e) high robustness delivery in which the drug is only active in the target
shown by some of the nanostructure materials (Gu- area of the body (for example, in cancerous tissues or
nasekera et al., 2009). In recent years, the use of metal other diseased tissues) and sustained release formu-
nanoparticles has expanded in biomedical research. lations in which the drug is released over a period of
They are used in diagnosis and therapeutics due to time in a controlled manner from a formulation.At
their unique properties of high reactivity to the living present, there are 30 main drug delivery products on-
the market. The total annual income for all of these is

128
approximately US$33 billion with an annual growth tained or pulsatile drug release. Sustained release is
of 15 % (based on global product revenue). The rea- used to achieve a constant release of a drug over an
sons for this increasing interest in drug delivery are extended period of time. For example, many drugs
due to the increasing need of safe drugs, capable of have an optimum range of concentrations that if
reaching the target and with minimal side effects. the concentration of the drug is above or below this
In fact the main problems associated with system- range, the drug is toxic or has no therapeutic effect,
ic drug administration are essentially related to the respectively (Fig.1).
bio-distribution of pharmaceuticals throughout the
body. This indiscriminate distribution means that, Development of nonocarriers is a novel area of
to achieve a required therapeutic concentration the science thatprovides, with a new hope, the tools and
drug has to be administered in large quantities, the technology to work at atomic, molecular and supra-
major part of which is just wasted in normal tissues. molecular levels leading to creation of devices and
Ideally, a ‘‘perfect’’ drug should exert its pharmaco- delivery systems with fundamentally new proper-
logical activity only at the target site, using the lowest ties and functions. These carriers offer a number of
concentration possible and without negative effects advantages making it an ideal drug delivery vehi-
on non-target compartments (Pierige et al., 2005). cle.Drug release and transport are major factors for

The process for delivering a drug is as important


as the actual activity of the drug in determining the
therapeutic effect. For optimum therapeutic effect,
the right amount of a drug needs to get to the right
place at the right time. Consequently, advanced drug
delivery formulations have been developed over the
past 20 years that do not simply release a drug at a
specific rate, but release the drug in a way that the
pharmaceutical scientists and engineers have de-
signed. Additionally, because drug delivery can im-
prove safety, efficacy, convenience and patient com-
pliance, improving delivery methods has become a
major focus of pharmaceutical companies. In tradi-
tional drug delivery, common delivery routes include
oral, pulmonary, transdermal and injection, and they
each have certain advantages and disadvantages as-
sociated with them. For instance, all of these routes, Fig.2. Schematic diagram of theranostic gold nanoparticle.
except for direct injection into a vein or muscle tis-
sue, have cellular layers that are encountered, which creating an efficient DDS (Drug Delivery System).
function as a barrier to transport into the systemic Nano-carriers can be loaded with drugs through
circulation. Controlled release in drug delivery can non-covalent interactions or by covalent conjuga-
tion.Gold nanoparticles are suitable for the delivery
of the drugs to cellular destinations due to their ease
of synthesis, functionalization and biocompatibili-
ty. Gold nanoparticles functionalized with targeted
specific biomolecules can effectively destroy cancer
cells or bacteria (Fig. 2) (Duncan et al., 2010). Large
surface to volume ratio of gold nanoparticles offer a
large number of drug molecules being carried by the
gold nanoparticles (Grace and Pandian 2007). Gold
nanoparticles have been used for the co-adminis-
tration of protein drugs due to their ability to cross
cellular membranes, possibly due to the interaction
of gold nanoparticles with cell surface lipids.Surface
modification of gold nanoparticles would present
four major benefits, (i) it could increase the circula-
tion lifetime of conjugates by preventing or slowing
their removal by Reticulo-Endothelial System (RES),
(ii) drug molecules could specifically located and at-
tach to targeted cells, (iii) the stability could be im-
proved and (iv) the non-specific cytotoxicity could be
Fig.1. Schematic illustration of potential applications of reduced by capping gold nanoparticles (Fig.3).
gold nanoparticles in biology and medicine. One of the greatest challenges facing chemothera-
significantly enhance the therapeutic effect of a drug. py today is developing drug delivery systems (DDSs)
Typically, controlled release is used to achieve sus- that are efficacious and have therapeutic selectivity.
Both passive and active targeting approaches have
129
toid arthritis, and so forth, while considerable re-
search is currently going on for unveiling potential
anticancer and antimicrobial and biodiagnostic ap-
plications of Au-based materials and compounds for
clinical applications.
In the recent years, nanotechnology has attracted
most of the scientific community concerning the ap-
plications of nanotechnology in medicine. One par-
ticularly exciting field of research involves the use of
AuNPs for the diagnosis of cancer. AuNPs find signif-
icant exploitations in biomedical field due to:
➢ Their comparative chemical stability, making them
less hazardous,
Fig.3. Functionalized GNP’s (fGNP’s) for drug delivery.
➢ Simple and straightforward synthesis and fabrica-
been utilized with nanocarriers such as dendrimers, tion process, and
liposomes, metal nanoparticles, polymer micelles and
vesicles. These DDSs have improved in the targeted ➢ Genuine biocompatibility and non-interference
delivery of the therapeutics for cancer treatment. The with other labelled biomaterials (e.g. antibody and
application of gold nanoparticles (AuNPs) as a DDS is other biomarkers).
a rapidly expanding field (Gibson et al., 2007; Paciotti Furthermore, the advancement of nanotechnology
et al., 2006). Their inherent properties make them a has led researchers to generate nanostructures that
very promising vehicle for drug delivery. Controlled- can be conjugated to several kinds of biological mole-
fabrication of various sized particles (1–150 nm) with cules, including hormones and antibodies, which can
limited size dispersity has been established (Schmid reach targeted cells expressing the receptors. Colloi-
1992) and using ligand place exchange reactions dal Au has been playing an important role for cur-
(Templeton et al., 1999), multifunctionalmonolayers ing various diseasesalthough the exact mechanism of
can be fabricated. This structural diversity enables action is still poorly understood. Today, the applica-
particle surfaces to containmultiple targeting agents tions of AuNPs are increasing day by day in pharma-
and/or chemotherapeutics. ceutical sciences for human welfare. It can be used
The gold nanoparticles can also be used in an ul- to understand more about the nature of diseases like
trasensitive assay technique to detect cancers (Shipp cancer and HIV by providing significant target with
2006). Peng et al. (2009) introduced the functional- nano-vehicles.
ized gold nanoparticles in combination with the pat- 3.1 The advantages of using nanoparticles as a drug
tern recognition methods to diagnose the lung cancer delivery system include the following
from breath testing. This method is an in vitro sensor
array technique of the detection of biomarkers in ex- ➢ Particle size and surface characteristics of nanopar-
haled breath of lung cancer patients asa non-invasive ticles can be easily manipulated to achieve both pas-
diagnostic tool. In addition, Thaxton et al. (2009) sive and active drug targeting after parenteral admin-
reported the combination system based on the mag- istration.
netic microparticles and the gold nanoparticles con- ➢ They control and sustain release of the drug during
jugated with the prostate-specific antigen- (PSA-) the transportation and at the site of localization, al-
specific antibodies to diagnose prostate cancers. In tering organ distribution of the drug and subsequent
this system, the magneticmicroparticles conjugated clearance of the drug so as to achieve increase in drug
with PSA-specific antibodies were used to extract the therapeutic efficacy and reduction in side effects.
traceable amounts of PSA in the serum samples from
patients, and the gold nanoparticles with PSAspecifi- ➢ Drug loading is relatively high and drugs can be
cantibodies and short DNA sequences (the barcodes) incorporated into the systems without any chemical
were attached to detect this analyte for in vitro bar- reaction.
code assay. ➢ Site-specific targeting can be achieved by attaching
3. Role of Gold nanoparticles in nanobiotechnology targeting ligands to surface of particles or use of mag-
netic guidance.
Gold (Au) is unique compared to other metals be-
cause of its resistance to tarnishing. According to ➢ The system can be used for various routes of ad-
the earliest records, use of Au for medical purposes ministration including oral, nasal, parenteral, in-
can be traced back to the Chinese civilization in 2500 tra-ocular etc.
BC, and after that, several ancient cultures have uti- ➢ Avoidance of coalescence leads to enhanced phys-
lized Au-based materials for medicinal purpose for ical stability.
the treatment of a variety of diseases such as small-
pox, skin ulcers, measles, and syphilis. In today’s era ➢ Reduced mobility of incorporated drug molecules
of nanotechnology, gold nanoparticles (AuNPs) have leads to reduction of drug leakage.
been used for the treatment of diseases like rheuma- ➢ Static interface solid/liquid facilitates surface mod-
130
ification. ovarian cancer proceeded with tumorsSpecific folate
3.2 Disadvantages of nanoparticles receptor-αtargeted fluorescent agent (Van Dam 2011).
This study offers the potential application of intra-
3.2.1. Potential toxicity operative staging with tumor-specific fluorescence
While the small size of nanoparticle is what makes imaging in patients with ovarian cancer by folate
them so useful in medicine, it is also the factor that receptor-αoverexpression.
might make them potentially dangerous to human Gold nanoparticles based on gold cores are an-
health. otherversatile platform that provides desirable val-
uesfortheranostic systems (Chan et al., 2013). They
3.2.2. Environmental concerns are preparedwith core size from 1.5 to 10 nm, pro-
Artificially manufacture nanoparticles will be new to viding large areafor efficient drug and ligand conju-
the environment in type and quantity and would con- gations (Link and Al-Sayed 2002). Goldnanoparticles
stitute a new class of non biodegradable pollutants. are commonly synthesized by chemicaltreatment of
hydrogen tetrachloroaurate. The therapeutic load-
4. Ideal properties of nanoparticles ing are achieved by eithernon covalent interaction
➢ Natural or synthetic polymer (e.g. via electrostatic interaction)or covalent chem-
ical conjugation of (i.e., organic drug).The inherent
➢ Inexpensive features of gold nanoparticles include diagnostic
➢ Nontoxic property, tunable core size, mono dispersity, low tox-
icity, large surface to volume ratio, surface plasmon
➢ Biodegradable absorption, ability to bind to biomoleculesvia Au–S
➢ Nonthrombogenic bonds, light-scattering propertiesand ease of fabri-
cation (Connor 2005; Kumar et al., 2013). Recently,
➢ Nonimmunogenic gold nanoparticlesshowed the possibility of treating
➢ Particle diameter <100nm MDR tumors by targeted photothermal treatment in
combinationwith a chemotherapeutic agent (Lee et
➢ No platelet aggregation al., 2014). Heo etal. (2012) described gold nanopar-
➢ Noninflammatory ticles surface-functionalized with PEG, biotin, pa-
clitaxel and rhodamine B linked beta-cyclodextrin
➢ Prolonged circulation time (beta-CD) as theranostic platform. Paclitaxel formed
4.1 Applications of targeted delivery systems from inclusioncomplex with beta-CD which was then
cells to clinics conjugatedwith gold nanoparticles. In vitro studies
suggest that gold nanoparticles have higher affinity
Nano platforms generally have the potential to be towards cancercells such as HeLa, A549 and MG63
applied as cancer diagnosis, imaging, and treatment in comparisonto NIH3T3 cells. Furthermore, gold
in vitro and in vivo. Targeted delivery strategies of nanoparticles displayed significant cytotoxic effect
nano platforms are special formulations and carriers against HeLacancer cells.
with anticancer drugs such as pegylated liposomes, In another work, smart theranostic gold nanopar-
polymeric nanoparticles/micelles, and albumin- ticles were developed i.e., DOX was conjugat-
based drug carriers. These nanoplatforms that we ed togold nanoparticles via Au-S bond by using a
mentioned above can be applicable to the biomedical peptide substrate, Cys-Pro-Leu-Gly-Leu-Ala-Gly-
approaches such as cancer diagnostics (Kateb et al., Gly(CPLGLAGG), which is specifically cleaved by the
2011), anticancer therapy (Muthu and Wilson 2010), protease (Fig. 4). The animal studies showed thatafter
nano-imaging (Bulte and Modo 2007), bimodal injection of the functionalized gold nanoparticlesto
imaging (Jarzyna et al., 2010; Janczewski et al., 2011), the tumor-bearing mice, the over-expressed protease
and real-time intra-operative imaging (Van Dam et
al., 2011). The FDA has approved clinical use of a
significant number of anticancer drug products in
the nanometer size range including the applications.
In particular, nanoimaging has become based on the
diagnostic potential of an earlier detection in the
cancer and other human diseases (Jarzyna et al., 2010).
In the case of bimodal contrast imaging, bimodal
contrast agents allow the assessment of regions of
interest using two independent imaging modalities
such as MRI reagents and fluorescent agents. In the
case ofMRI and fluorescence imaging, MRI has an
excellent spatial resolution, and fluorescence imaging
compensates for the sensitivity of MRI overcoming
the limitations of a single-modality imaging (Jeff
and Bulte 2008). For intra-operative fluorescence Fig.4. Schematic presentation of site specific drug delivery
imaging, the first human trial in advanced-stage usingnanocarrier systems

131
in tumor tissue and intracellular glutathione haveled Their stability, tunable monolayers, functional flexi-
to the rapid release of DOX from the functionalized- bility, low toxicity, and ability to control the release
gold nanoparticles. Here, enhanced efficacy on tumor of drugs offer manypossibilities for further devel-
growth inhibition and fluorescent imaging wasreal- opment of DDSs. Additional investigations of these
ized simultaneously. The gold nanoparticles with- systemswill be required to fully understand their
stimulus responsive drug release property showed a pharmacokinetics, interactions with the immunesys-
promising smart theranostic application for concur- tem, and the extent of cytotoxicity due to surface and
rentcancer diagnosis and therapy (Chen et al., 2013). size of the AuNPs. Continuedresearch into these na-
noscale delivery vehicles will expand the understand-
5. Drug delivery strategies using gold nanoparticle ing of theinteractions of these materials with biologi-
platforms cal systems, and promoting the development ofmore
Drug release and transport are major factors for cre- effective DDSs.
ating an efficient DDS. Nano carriers can be loaded Conflict of interest statement
with drugs through non-covalent interactions or by
covalent conjugation (Torchilin 2001) using a pro- We declare that we have no conflict of interest.
drug that is processed by the cell (Morgan et al.,
2006). AuNPs provide an excellent platform for DDS References
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