Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5398_Библиотеки_им_академика_М_И_Перельмана.pdf
Targeted Drug Delivery: Principles and Strategies 69
Leali P, Quinti I, Cavaliere FM, Girelli G, Pietrogrande MC, Finocchi A, Tabolli S, Abeni D,
Magnani
M (2014) Intra-erythrocyte infusion
of dexamethasone reduces neurological symptoms in ataxia teleangiectasia patients: results of
a phase 2 trial. Orphanet J Rare Dis 9:5.
https://doi.org/10.1186/1750-1172-9-5
76. Christie C, Madsen SJ, Peng Q, Hirschberg H
(2015) Macrophages as nanoparticle delivery
vectors for photothermal therapy of brain
tumors. Ther Deliv 6(3):371–384
77. Rosales C (2018) Neutrophil: a cell with many
roles in inflammation or several cell types?
Front Physiol 9:113.
https://doi.org/10.
3389/fphys.2018.00113. PMID: 29515456;
PMCID: PMC5826082
78. Su Y, Gao J, Kaur P, Wang Z (2020) Neutrophils and macrophages as targets for development of nanotherapeutics in inflammatory
diseases. Pharmaceutics 12(12):1222.
https://
d o i . o r g / 1 0 . 3 3 9 0 /
pharmaceutics12121222. PMID: 33348630;
PMCID: PMC7766591
79. Han X, Wang Y, Han WD (2018) Chimeric
antigen receptor modified T-cells for cancer
treatment. Chronic Dis Transl Med 4(4):
225–243.
https://doi.org/10.1016/j.cdtm.
2018.08.002. PMID: 30603741; PMCID:
PMC6309024
80. Hoang VT, Forsyth NR, Heke M, Nguyen LT
(2022) Stem cell-based therapy for human diseases. Signal Transduct Target Ther 7(1):272.
https://doi.org/10.1038/s41392- 02201134-4. PMID: 35933430; PMCID:
PMC9357075
81. Cuiffo BG, Karnoub AE. Mesenchymal stem
cells in tumor development: emerging roles
and concepts. Cell Adh Migr. 2012 May-Jun;6(3):220–30. doi: 10.4161/cam.20875.
Epub 2012 May 1. PMID: 22863739;
PMCID: PMC3427236
82. Dovizio M,
Ballerini P, Fullone R, Tacconelli S,
Contursi A, Patrignani P (2020) Multifaceted
functions of platelets in cancer: from tumorigenesis to liquid biopsy tool and drug delivery
system. Int J Mol Sci 21(24):9585.
https://
doi.org/10.3390/ijms21249585. PMID:
33339204; PMCID: PMC7765591
Chapter 4
Nanotechnology in Drug Delivery: From Bench to Bedside
Mounil Mankad, Pranav Anjaria, Sanjay Vaghela, and Varun Asediya
Abstract
Nanotechnology enhances drug delivery by improving efficacy, specificity, and safety through nanoparticles.
Nanoparticles can be tailored for specific applications and offer advantages like precise drug release control
and enhanced targeting. Nanotechnology addresses challenges in traditional drug delivery methods and
enables smart drug delivery systems, polymer-drug conjugates, multifunctional drug carriers, and organic/
inorganic composites. Nanoparticulate drug delivery systems like liposomes and microemulsions provide
controlled drug release and improved therapeutic outcomes.
Key words Nanotechnology, Drug delivery, Nanoparticles, Targeted delivery, Controlled release
1 Introduction
In recent decades, the field of nanotechnology has emerged as a
powerful tool in revolutionizing various aspects of medicine, particularly drug delivery. The ability to manipulate matter at the
nanoscale has opened up new avenues for the development of
novel therapeutics, enhancing their efficacy, specificity, and safety
profiles [
cal sciences has led to the birth of nanomedicine, a rapidly evolving
interdisciplinary field with profound implications for healthcare.
The primary objective of drug delivery systems is to transport
therapeutic agents to their target sites within the body in a controlled manner, maximizing therapeutic efficacy while minimizing
side effects [
challenges such as poor bioavailability, off-target effects, rapid
clearance, and systemic toxicity. Nanotechnology offers promising
solutions to overcome these limitations by providing platforms for
precise control over drug release kinetics, improved targeting capabilities, and enhanced biocompatibility [
nanoparticles, which are typically in the size range of 1 to 1000
1]. This integration of nanotechnology with pharmaceuti-
2]. Traditional drug delivery approaches often face
3].
At the heart of nanotechnology-based drug delivery systems lie
71
72 Mounil Mankad et al.
nanometers. These nanoparticles can be engineered from a variety
of materials including polymers, lipids, metals, and inorganic substances, each offering unique properties and functionalities [
tailoring the physicochemical characteristics of nanoparticles,
researchers can fine-tune their behavior in biological systems,
enabling customized drug delivery strategies for specific therapeutic applications. One of the key advantages of nanoscale drug
delivery systems is their ability to exploit the unique biological
properties of tissues and cells [
passively accumulate in
meability and retention (EPR) effect, a phenomenon characterized
by leaky vasculature and impaired lymphatic drainage in solid
tumors. This passive targeting mechanism allows for preferential
accumulation of drugs in tumor sites, thereby improving therapeutic outcomes while minimizing systemic exposure and associated
toxicities [
gies where nanoparticles are functionalized with ligands that can
selectively bind to receptors overexpressed on the surface of diseased cells. This molecular targeting approach enhances the specificity of drug deliver y, enabling precise localization of therapeutics
to their intended targets. Such targeted delivery systems hold
immense promise for the treatment of various diseases, including
cancer, inflammatory disorders, infectious diseases, and neurological disorders. In addition to targeted delivery, nanotechnology
offers opportunities for controlled drug release, allowing for spatiotemporal modulation of drug concentrations at the site of
action. By encapsulating drugs within nanoparticles or conjugating
them to nanoparticle surfaces, researchers can design formulations
with tunable release kinetics, enabling sustained drug release over
extended periods [
improves therapeutic efficacy but also reduces the frequency of
dosing, enhancing patient compliance and convenience. Despite
the tremendous potential of nanotechnology in drug delivery, several challenges remain to be addressed. These include concerns
related to nanoparticle stability, scalability of manufacturing processes, regulatory considerations, and long-term safety profiles.
Overcoming these hurdles requires concerted efforts from multidisciplinary teams comprising chemists, biologists, engineers, clinicians, and regulatory experts [
4]. By
5]. For instance, nanoparticles can
tumor tissues through the enhanced per-
6].
Furthermore, nanotechnology enables active targeting strate-
7]. This controlled release capability not only
8, 9].
2 History
The history of nanotechnology in drug delivery traces back to the
mid-nineteenth century when Petros and his colleagues reported a
study on the subject. However, significant advancements began to
emerge in the latter half of the twentieth century. In 1955, a pivotal
Nanotechnology in Drug Delivery: From Bench to Bedside 73
development occurred with the conjugation of polymers and drugs,
marking an important milestone. This breakthrough was followed
by the appearance of the first controlled-release polymer device in
1964, providing a means for sustained drug delivery [
the
discovery of
liposomes by Bangham laid the groundwork for
10
]. I
n 1965,
liposome-based drug delivery systems. Subsequent years saw further advancements, including the report of albumin-based nanoparticles in 1972 and the formulation of liposome-based drugs in
1973. The momentum continued in the 1980s, with the formulation and approval of the first micelle in 1983, showcasing the
potential of nanotechnology. In 1989, the FDA granted approval
for the first control
in pharmaceutical sciences.
led formulation, signaling growing recognition
The 1990s witnessed a watershed
moment with the entry of the first polyethylene glycol (PEG)
conjugated with protein into the market in 1990, offering
improved stability and prolonged circulation times. These advancements underscore the evolution of nanomedicine, reflecting its
transformative impact on healthcare delivery [
of nanoparticles from
Recent advances are shown in Fig.
1991 to 2022 is described in detail in Table
1.
11]. The evolution
1.
3 Classification of Nanotechnology (Nanomaterials/ Nanoparticles)
Nanotechnology encompasses a wide range of materials and structures engineered at the nanoscale, each with unique properties and
2.). Nanoparticles, in particular, play a crucial role
27, 28]. Each category offers distinct char-
3.
3.1 Organic Nanoparticles
applications (Fig.
in various fields including medicine, electronics, energy, and environmental remediation. These nanoparticles can be classified based
on their chemical proper ties into three main categories: organic,
inorganic, and carbon [
acteristics and functionalities, catering to diverse applications and
research endeavors. Different types of nano drug molecules are
shown in Fig.
Organic nanoparticles are composed of carbon-based compounds,
often containing elements such as carbon, hydrogen, oxygen, and
nitrogen. These nanoparticles are typically synthesized from
organic polymers, dendrimers, or lipid-based materials
29]. Organic nanoparticles offer several advantages, including
[
biocompatibility, tunable surface chemistry, and facile functionalization. They find extensive use in biomedical applications such as
drug delivery, imaging, and tissue engineering. Lipid-based nanoparticles, such as liposomes and lipid nanoparticles, are widely
employed as drug carriers due to their ability to encapsulate hydrophobic drugs and facilitate their targeted delivery [
ally, polymeric nanoparticles, such as poly (lactic-co-glycolic acid)
30]. Addition-
74 Mounil Mankad et al.
Table 1
Evolution of nanoparticles from 1991 to 2022
Year Types of NPs Drug delivery approach Application References
1991 Poly-alkyl-
cyanoacrylate
nanoparticles
1992 Calcium
hydroxyapatite
ceramic (CHC)
1995 Poly-alkyl-
cyanoacrylate
(PECA)
nanoparticles
1996 Protein and
peptides-based
NPs
2000 Liposome with
hyperthermia
as nanoparticles
2001 PEGylated poly-
cyano-acrylate
nanoparticles
Carrier that delivers drug to
target specific site
Drug gentamicin placed in
the porous blocks of
calcium hydroxyapatite
antibiotics (CHA)
Ofloxacin (OFX) and
perfloxacine entrapped in
PECA nanoparticles. OFX
system more efficient
than PFX system
Monoclonal antibodies,
recombinant
transported to BBB by
chimeric
peptide approach
Increased drug
tumor
Hyperthermia helps liposome
to work properly
Efficient drug
deliver therapeutic
molecules in prion disease test
proteins
delivery
carrier
to
to
Cancer chemotherapy and
intracellular
antibiotherapy
The bactericidal activity was
retained and drug
shows effective results
The fluoro-quinolone-loaded
nanoparticles
enhance antimicrobial activity
of the
drug
Avidin conjugate with BBB
vector to
proteins across
Vasoactive intestinal peptide
cures brain diseases
Helpful in human cancer
treatment
Long retention time in blood
as compared to
non-PEGylated
Brain
target tissues show uptake
higher in
scrapie-infected animals
transport all
BBB.
nanoparticles.
and spleen
[10]
[12]
[13]
[14]
[15]
[16]
2002 Transferrin-
mediated
receptor
endocytosis
2005 Liposomes,
nanoparticles
Transferrin and transferrin
receptor in drug and
in gene transference via the
BBB
Vitamin folic acid placed
inside cationic
liposomes and
liposomes to folate
ligand act
chemotherapeutics
agents, and DNA attaches to
the
receptor-bearing cancer cells
in vitro
conjugate
as carrier and
Transferrin receptor interceded
iron uptake;
regulation of transferrin
receptor expression;
anticancer drugs site-specific to
tumor cells
Folate-associated, lipid-based
nanoparticles
transport DNA with high
transfection efficacy and
constraining tumor progress
with intratumoral
shot into human
nasopharyngeal and prostate
malignancy using an HSV-tk/
GCV
treatment system
[17]
[18]
(continued)
Nanotechnology in Drug Delivery: From Bench to Bedside 75
Table 1
(continued)
Year Types of NPs Drug delivery approach Application References
2007 Gold nanoparticles
(AuNPs)
2010 Mesoporous silica
nanopar
2013 Silver nanoparticle Nanoparticles of noble metal
2015 Polyamidoamine
ticles
nanopar
ticles
Drug and gene delivery
approach to deliver
drugs and genes by using
gold nanoparticles.
The transfection efficacy for
beta galactosidase
with various MMPCs
Targeted carriage of
chemotherapeutic
mediator
methotrexate (MTX) to
tumor cells by means of poly
(ethylene
mine)-functionalized
mesoporous silica
small units as vectors for drug
delivery
potential as
show
photo-activated vectors for
drug delivery. SNPs
conjugated with thiol-
terminated photo-liable
DNA oligonucleotides
Polyamidoamine
nanoparticles work as
nanocarrier and deliver anti-
malarial drug to
the targeted sites. It also
works
as nanomedicine
Properties of drug transfer like
reduced
treating acute diseases, uptake
and release rate
using fluorophore AuNPs
provide added insight
in future
Choice of adaptable sur
functionalization;
High level of cell specificity and
effective
cellular uptake;
A slight grade of early seepage
and the
measured release of the
medicine; Low
cytotoxicity of the transporter
Good consistency to nucleases,
hybridization
amplified
release, and effective
cellular uptake as associated to
commercial
transfection vectors
Union of doxorubicin and
polymers
drug solubility, enhances its
blood half-life,
decreases toxicity, and
enhances targeting
toxicity,
face
action upon photo
increases
[19]
[20]
[21]
[22]
2017 Filamentous
bacteriophage
and
phage-
mimetic
nanoparticles
Delivery of drug and gene
through
particles. Phage can be
chemically altered or
genetically designed to load
drugs and transfer
foreign genes
phage
Filamentous bacteriophage
used
in the making of
medicine transfer as virus-
based delivery
system. The bacteriophage
uncovered with
mark-definite peptides or
antibodies can be bound
with other carriers (such as
liposomes, inorganic
NPs) to make a unique transfer
scheme
[23]
(continued)
76 Mounil Mankad et al.
Table 1
(continued)
Year Types of NPs Drug delivery approach Application References
2020 Mesoporous silica
NPs with
folic acid
(MSN-COOH-
Tet-HBP-FA)
2021 Novel silver
nanoparticles
2022 1-Iridium oxide
NPs
2-Chitosan
nanopar
ticles
This approach is pH subtle
ug delivery
dr
system built on folic-acid-
targeted HBP to
reform/reshape the
mesoporous
silica nanoparticles
In this approach, DNA or
messenger RNA
(mRNA) sequences are
transported to the body
to produce proteins, which
copy disease
antigens to arouse the
immune response
A nanoprobe was synthesized
for in vivo
fluorescence tomography of
microRNA and
coactive photothermal
dealings of lump.
It is a biotic macromolecule-
based medicine
transfer system to advance the
curative
potential of non-natural
neural
control networks
The hyper-branched polymer
HBP
encapsulates
the drug particles in the
mesopores as a lid, which
progresses the permanency of
the carrier material
and permits the drug to attain
“zero pre-release”
within 20 h in a usual
physiological atmosphere
The nucleic acid vaccines
comprise
and humoral immunity
activation, affluence of
strategy, quick malleability to
altering pathogen
strains, and customizable
multi-antigen vaccines.
To fight the SARS-CoV-
2 epidemic and many
other ailments, nucleic acid
vaccines seem to be a
hopeful way
Nanoprobe helped in vivo in
healing
continuously killed the lump
growth.
These neuroprotective
mediators are merged into
the structure of NGCs and
delivered into brain via
NPs
cell-mediated
studies and
[24]
[25]
[26]
3.2 Inorganic Nanoparticles
(PLGA) nanoparticles, offer controlled release properties and can
be tailored to achieve desired drug release kinetics. Organic nanoparticles also hold promise in other fields such as catalysis, sensors,
and nanoelectronics [31].
Inorganic nanoparticles consist of materials that lack carboncarbon bonds and are typically composed of metals, metal oxides,
semiconductors, or ceramics. These nanoparticles exhibit unique
physical and chemical properties such as high surface area, optical
Nanotechnology in Drug Delivery: From Bench to Bedside 77
Fig. 1 Recent
engineering
advances
in the development of nanoparticles in biomedical
Fig. 2 Applications of nanomedicine
78 Mounil Mankad et al.
Fig. 3 Types of nano drug molecules
properties, and catalytic activity [32]. Inorganic nanoparticles can
be synthesized through various techniques including chemical precipitation, thermal decomposition, and sol-gel methods. Examples
of inorganic nanoparticles include gold nanoparticles, silver nanoparticles, iron oxide nanoparticles, quantum dots, and titanium
dioxide nanoparticles [
prized for their optical
making them valuable in biomedical imaging, sensing, and cancer
therapy. Iron oxide nanoparticles are widely used as contrast agents
in magnetic resonance imaging (MRI) and as therapeutic agents for
magnetic hyperthermia-based cancer treatment. Inorganic nanoparticles also find applications in catalysis, environmental remediation, and energy conver
3.3 C
arbon-Based
Nanoparticles
Carbon-based nanoparticles are composed primarily of carbon
atoms arranged in various nanostructures such as fullerenes, carbon
nanotubes (CNTs), graphene, and graphene oxide. These nanoparticles exhibit exceptional mechanical, electrical, and thermal properties, rendering them highly versatile for a myriad of applications.
Fullerenes, spherical carbon molecules comprising hexagonal and
pentagonal rings, possess unique cage-like structures and are
33
]. Gold nanoparticles, for instance, are
properties and surface plasmon resonance,
sion and storage [
34].