Vol 4, Issue 2, 2022 (347-359)
http://journal.unpad.ac.id/idjp
*Corresponding author,
e-mail : amalia@unpad.ac.id (E. Amalia)
https://doi.org/10.24198/idjp.v4i1.35312
2022 E. Amalia et al
Nanoparticle Drug Delivery System
Eri Amalia*1, Auliya Afinasari2
1 Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy,
Universitas Padjadjaran, Indonesia
2Bachelor of Pharmacy Study Program, Faculty of Pharmacy, Universitas Padjadjaran,
Indonesia
Submitted : 22/07/ 2022, Revised : 01/08/ 2022, Accepted : 06/06/2023, Published : 16/08/2023
Abstract
A drug delivery system (DDS) is a type of drug formulation specifically designed
to include the drug in a vesicle or suitable compartments that aims to deliver the
active substance to achieve its target in the body. Current technology of DDS has
evolved from conventional to targeted delivery systems including nanorobots, gene
therapy, biological products, and long-term delivery systems. Among the DDS that
have been developed, nanotechnology has been applied in several treatments
including for cancer and antifungal treatment. This review is focused on elaborating
the basic principles, strategies, and carrier systems employed in the application of
nanotechnology specifically liposomes, dendrimers, niosomes, micelles, solid-lipid
nanoparticles, nanospheres, nanocapsules, and gold nanoparticles. The data were
collected from 41 primary published journals and 22 supporting literature. DDS is
specifically formulated for specific therapy. The design including the selection of
polymeric or natural encapsulation material and its manufacturing technology that
can be applied to fulfill the criteria of specific nanoparticle characteristics.
Keywords: Drug Delivery System, Nanotechnology, Nanoparticle, Liposome,
Dendrimer.
1. Introduction
A drug Delivery System (DDS) is a
method of drug formulation, which aims to
deliver active substances to achieve
therapeutic effects in the body. Several
types of DDS are currently developed with
the main concern to achieve suitable
absorption, distribution, metabolism, and
elimination (ADME) of a drug and are
closely related to influencing the
performance and therapeutic effect of a
drug (1). Different from conventional
medicine, DDS shows proven to improve
its performance due to its capability to
deliver the drug reaching its target, thus
maximum efficiency of therapy is achieved
(2). Currently approved medicines have a
good profile suitable to pharmacopeia
standard for its specific purpose,
nevertheless, some drugs could be further
developed to overcome the weakness of
E. Amalia et al / Indo J Pharm 4 (2022) 347-359
348
conventional dosage form in terms of their
pharmacokinetic aspects such as low half-
life, and high volume of distribution;
Pharmacodynamics such as low
specification and low therapeutic index;
Pharmaceuticals such as low solubility and
stability; and Pharmacotherapeutics such as
high doses, adverse effects, and low patient
compliance (3).
The structure of DDS is formulated
with a specific vesicle or compartment
structure to allow the drug entraped or
encapsulated into it thus able to penetrate to
lipid bilayer membrane of the cell surface
and function in biological system suitable
to its intended therapeutic effect, with high
specificity, better biodistribution, lower
toxicity, and better efficacy. It is also
exhibit its superior protection of drugs
from degradation or rapid clearance (4,5).
Depending on its purpose, the
flexibility of DDS designed is vary from
nano to micrometer size of particles.
Nevertheless the scope of nanoparticle
DDS limit its size specific 1-100 nm, with
several type including liposomes,
dendrimers, niosomes, micelles, solid-lipid
nanoparticles, nanospheres, nanocapsules,
and gold nanoparticles (6). Several aspects
must be considered during DDS
preparation including selection of its type
refer to its intended used, formulation and
selection of material, preparation
technique. This review article discus the
above-mentioned aspect as one of the
reference of researcher working in the
nanoparticle.
2. Method
The data were collected from
electronic databases, consisted primary and
secondary sources including research
journals, article reviews, and scientific
articles from international journals as the
main data source such as PubMed, Elsevier,
and others. The data obtained are published
in the last 10 years. The search for data
sources used the keywords "drug delivery
system", "history and evolution drug
delivery system" and "nanoparticle drug
delivery system” then the search is
manually performed according to the
relevant libraries. This research shows each
nanoparticle’s components, properties,
materials, and formulation in general.
3. Result and Discussion
3.1 History and Evolution of Drug
Delivery System
Nowadays, three generation of
Drug Delivery System (DDS) its evolution
are categorized. It began in 1952 with the
development of the slow-release
Spansule® as the first generation of DDS to
deliver drugs for 12 hours after oral
administration through an initial dose
followed by a continuation release.
Furthermore, this technique was successful
in controlling the physicochemical
properties of delivery systems with oral and
transdermal formulations in the 1980s
providing a therapeutic duration of up to 24
hours for the small molecules that dominate
the drug delivery sector and market. In this
first generation, drugs were developed in
the form of enteric-coated and delayed-
release dosage technologies including
pellets (7).
The second generation started
approximately after 1980 to around 2010
with the development of long-term
injections and implants in 1989, also the
first delivery of proteins and peptides in
1990. In addition, the introduction of
polymer-drug complexes as controlled
delivery systems (such as osmotically,
swelling and diffusion) was started in the
second generation. Furthermore, in the
third generation that began from 2010,
targeted delivery systems were introduced
as targeted, modulated, and self-regulated
drugs with the development of
nanoparticles, gene therapy, biological
products, and long-term delivery systems
reaching 6-12 months (8). This latest
generation began to developed its utility for
aimed vaccines and Covid-19 treatment
including the development of a transdermal
Covid-19 vaccine with microneedles.
E. Amalia et al / Indo J Pharm 4 (2022) 347-359
349
While in the treatment of Covid-19, drug
delivery is developed to the target site using
nanoparticles, specifically gold
nanoparticles (9,10). Despite its numerous
advantages, the nanoparticle remain has
limitation including difficulties of
maintaining its stability of structure and
used of large organic solvent to prepare its
structure (11,12).
3.2 Types of Drug Delivery System Nanoparticles
Figure 1. Types of several drug delivery systems
Liposomes
Liposomes are small vesicles with a
phospholipid bilayer membrane that can
deliver both hydrophilic and hydrophobic.
Liposomes have a similar structure of cell
membranes; thus, liposomes are able to
penetrate cell membranes efficiently.
Liposomes have some of advantages that
can be utilized either for ocular, injection or
oral DDS including the half-life of the
vesicles and protecting the active drug
substance with the liposome structure from
degradation in the stomach (13).
Furthermore, liposomes will increase the
biodistribution of compounds to the target
site and minimize systemic toxicity (14).
The advantages of liposomes generally
have been used in vaccine delivery, gene
delivery, molecular imaging, and genome
editing (15).
Liposomes could be forming
naturally, specifically amphiphilic
phospholipid molecules that spontaneously
form lipid bilayers around an aqueous
medium (15). Moreover, liposomes can be
also prepared in the laboratory by various
methods, including thin-film hydration,
reverse phase evaporation and
proliposomes. The thin-film hydration
method is commonly used because its
simple preparation method. This method
involves dissolving liposome-forming
materials (phospholipids or cholesterol) in
organic solvents (chloroform) by
evaporation with a rotary evaporator to
form a thin lipid layer. Subsequently, the
thin layer was rehydrated with the aqueous
phase to become a suspension of liposome
particles, then the final suspension is
E. Amalia et al / Indo J Pharm 4 (2022) 347-359
350
completed by sonicating to reduce the
particle size (16).
One of the marketed liposomes as
DDS is Doxil® (Doxorubicin HCl
liposome injection that is used for ovarian
cancer, AIDS and myeloma treatment. The
preparation of this medicine including the
materials is approved by the FDA since
1995. Each vial (10 mL or 30 mL) contains
20 mg or 50 mg of doxorubicin HCl with a
liposome carrier consisting of N-(carbonyl-
methoxy polyethylene glycol 2000)-1,2-
distearoyl-sn-glycero3-
phosphoethanolamine sodium salt (MPEG-
DSPE), 3.19 mg/mL; fully hydrogenated
soy phosphatidylcholine (HSPC), 9.58
mg/mL; and cholesterol, 3.19 mg/mL. Each
mL also contains ammonium sulfate,
histidine as a buffer, hydrochloric acid for
pH control, and sucrose to maintain
isotonicity. Liposomes encapsulated more
than 90% of the drug (17).
The FDA has also approved other
preparations and materials with DDSs
liposomes that have been marketed for
cancer therapy, including DaunoXome®
(liposomal daunorubicin (non‐
PEGylated)), Myocet® (liposomal
doxorubicin (non‐PEGylated)), Marqibo®
(liposomal vincristine (non‐PEGylated)
PEGylated)), MEPACT® (liposomal
mifamurtide (non‐PEGylated)), and
Onivyde MM‐398® (liposomal irinotecan
(PEGylated)). In addition, there are also
liposome formulations for vaccines
including Epaxal® (liposomes with
hepatitis A virus) and Inflexal V®
(liposomes with trivalent-influenza); For
anesthesia including Diprivan® (liposomal
propofol); and for the treatment of the
fungus AmBisome® (liposomal
amphotericin B) (18).
Dendrimers
Dendrimers are spherical repeating
branched nanostructures with three section:
a core group, a branched chain, and a
terminal functional group that subsequently
conjugated with various ligands (19).
Dendrimer has beneficial properties
including hyperbranched dendrimer
structure, well-known molecular weight,
size, and globular shape, monodisperse
properties, and a multifunctional surface
thus can be utilized as DDS to increase drug
solubility, cancer treatment, cell delivery,
and RNA introduction. Dendrimer is
performed either by involving hydrogen or
covalent bonds. Hydrogen bonds will trap
the drug in the dendrimer structure while
covalent bonds will form the interaction
between the drug with the dendrimer
surface. Furthermore, dendrimer developed
to encapsulating drugs with the core
structure of the dendrimer that occurs in a
nonbonding pair (20).
The preparation of the dendrimer
generally prepared in two ways, the
divergent method and the convergent
method. The divergent method involves
repeated steps of forming branch or
monomer units around the core structure.
One of the dendrimers that uses the
divergent method approach is The
PAMAM (PolyAmidoamine) dendrimer.
PAMAM is one of the dendrimers that has
been commercially produced and applied
that consists 0 to 11 generations with
different properties, including size,
structure, molecular weight, solvent-
accessible surface area, and monomer
distributions. The preparation of PAMAM
was initiated by synthesizing the branch
structure with Michael addition from the
acrylate ester to the ammonia core, then
amidation with the excess of ethylene
diamine (EDA). The initial step will result
in a half generation and the addition of
diamine results in a full generation. The
core initiator of PAMAM is an ammonia
molecule or EDA. The dendrimer core
synthesis was carried out in two sequential
steps: Michael addition of primary amine,
and EDA to methyl acrylate followed by
the amidation of tetra-ester formed with
EDA. The tetra-ester itself is considered a
0.5 generation PAMAM dendrimer and the
early EDA is considered a first generation.
Amidation of the tetra-ester with EDA
E. Amalia et al / Indo J Pharm 4 (2022) 347-359
351
results in a zero-generation dendrimer with
four terminal amino groups. Repeating the
two-step procedure resulted in higher
dendrimer generation (21).
For the convergent method, the
preparation began with the synthesis
between branches of the same monomer on
the outside that finishes up by attaching the
monomer to the core structure. One of the
dendrimers that have been commercialized
using the convergent synthesis method
approach is the 5th generation PPI
(PolyPropylene Imine) dendrimer that has a
primary amine on the surface group and
tertiary tris-propylene amines inside
(22,23).
One of the DDSs with a dendrimer
preparation that have been published is
DEP® docetaxel developed by the
pharmaceutical company Starpharma. The
drug is intended for breast cancer treatment
and consists a type of PEGylated polylysine
dendrimer with the active substances
conjugated to its surface. DEP® docetaxel
is currently still in the pre-clinical phase 2
trial (24,25).
Niosomes
Niosomes are nanocarriers with an
amphiphilic arrangement consisting of a
nonionic surfactant and cholesterol or other
amphiphilic molecules. Niosomes have a
structure similar to liposomes, the
difference is that liposomes consist of
phospholipids, which contain two
hydrophobic tails while niosomes consist of
non-ionic surfactants, which usually
contain one hydrophobic tail. Niosomes can
be unilamellar or multilamellar, so they can
carry hydrophilic and lipophilic substances
to the target site. Niosomes have low toxic
properties, require fewer production costs,
and are stable over long periods under
different conditions. Niosomes can carry
high concentrations of drugs to the target
thereby increasing the therapeutic effect,
high selectivity to reduce adverse side
effects and increase bioavailability, and are
suitable for many routes of administration,
including dermal, transdermal, ocular,
parental, pulmonary, and oral (26).
Niosomes preparation can be
carried out by several methods such as
micro-fluidization, sonication, dehydration
and rehydration, reverse phase evaporation,
transmembrane pH gradient, and thin layer
hydration (27). The thin layer hydration
method is a method commonly used in
niosomes preparation. Similar to
liposomes, niosomes preparation using this
method involves an evaporator by mixing
vesicle-forming materials such as
surfactants and cholesterol dissolved in the
volatile solvents chloroform and ethanol
(1:2) in a round bottom flask. Then the
organic solvent is removed using a rotary
evaporator which will leave a thin layer of
the solid mixture on the walls of the flask.
Dry surfactant films can be rehydrated with
10 mL aqueous phase (buffer pH 7.4) at 0-
60 °C with gentle stirring. This process
forms the characteristic multilamellar
niosomes (28,29).
Products that have been marketed
with niosomal formulations are generally
for cosmetics with the oldest product being
Lancome® from Loreal. As for therapeutic
drugs, various dosage forms and types of
drugs have been developed, one of which is
Piroxicam Niosomal Gel which has been
proven as a non-steroidal anti-
inflammatory drug (NSAID) that exhibits
anti-inflammatory, antirheumatic,
analgesic, and antipyretic activity in
animals. . This preparation is made by
dissolving a mixture of surfactant and
cholesterol in chloroform which is then
evaporated using an evaporator for niosom
preparation. Then niosome were added with
saline phosphate buffer, Sodium Phosphate
Buffer (PBS) (pH 7.4) containing
piroxicam (30,31).
Micelles
Micelles are polymers of 10-100 nm
in size which are formed from lipid
molecules that form spherical in solution,
making micelles amphiphilic. With the
hydrophobic nature of the micelle core, the
E. Amalia et al / Indo J Pharm 4 (2022) 347-359
352
solubility of water-insoluble drugs can be
increased, their release can be maintained,
and the permeability through biological
membranes can be increased. Micelles can
also increase bioavailability, also minimize
degradation and drug loss because micelles
protect against environmental influences.
Drug release from micelles is influenced by
several factors, micellar stability, drug
diffusion rate, partition coefficient, drug
concentration, as well as physicochemical
characteristics of the drug. In addition, pH,
temperature, ultrasound, and light can
increase the rate of drug release (32). The
small size of micelles allows micelles to
enter the blood circulation, tissue
penetration, and cellular uptake. Therefore,
micelles can be applied for anticancer drug
delivery by enhancing drug performance
leading to high accumulation in the target
(33). Micelles can be formed with
surfactants or block copolymers. The
hydrophobic moiety may use poly-β-
benzyl-L-aspartate, poly(DL-lactic acid),
poly(e-caprolactone), or anything that
protects the water-insoluble part from the
aqueous phase environment. For the
hydrophilic part, it can be in the form of
polyvinyl alcohol, poly (aspartic acid), and
others which can maintain hydrophilic
properties so that the stability of the
micelles will be maintained. The most
common methods for micellar preparation
are oil-in-water emulsion, solvent
evaporation, solid dispersion, and the
dialysis method (34). The dialysis method
is simple and commonly used in
laboratories. In this process, the copolymer
and the active substance are dissolved in an
organic solvent. Then the organic solvent
with high polarity will gradually be
dialyzed to be replaced by water, and the
polymer will be bound to precipitate into
the micelles (35).
One of the products with the
micellar formulation is Genexol-PM®
which is produced by the Samyang
Company. Genexol-PM® is a paclitaxel
that has been approved in South Korea for
the treatment of breast cancer and Non-
Small Cell Lung Cancer (NSCLC). The
drug consists of a low molecular weight
amphiphilic block copolymer,
monomethoxy Poly(D,L-lactide)-PEG-
methyl ether (MPEG-PDLLA), and
paclitaxel (36).
Solid-Lipid Nanoparticles
Solid Lipid Nanoparticle (SLN) is a
new drug delivery system consisting of a
solid lipid matrix and a water-dispersed
surfactant with a particle size of 10-
1000nm. The small size with a large surface
area makes it easier for SLNs to deliver
drugs to specific targets. SLNs can deliver
both hydrophilic and hydrophobic drugs.
The delivered drug will be inserted into a
solid lipid matrix so that it is protected from
the environment (for example, the digestive
tract) and degradation by enzymes (37,38).
In addition, SLN also has several
advantages, such as increasing the oral
bioavailability of lipophilic drugs due to the
solid state of the lipid matrix and the
formation of a layer or coating on the skin
which exhibits occlusive properties (39,40).
Several methods SLN
preparation are available including by
High-Pressure Homogenization (HPH)
(hot/cold), oil/water (o/w) microemulsion
breakdown, solvent injection method,
water/oil/water (w/o/ w) double emulsion,
ultrasonication, etc. (41). The HPH method
is the most frequently used, using high
pressure to reduce the size. This method
starts by heating the phase above the lipid
and drug to 5-10 °C the melting point of the
lipid phase, this causes the drug to be
dissolved or dispersed in the melted lipid.
Then the aqueous phase and surfactant were
added to the lipid mixture at the same
temperature. Then the hot pre-emulsion
obtained was homogenized using high-
quality tools. During this process, the
temperature is maintained at 70 ± 0.5 °C (or
as directed) under high pressure to prevent
the lipids from hardening. Then the o/w
nano-emulsion was immediately formed to
produce SLN (42,43).
E. Amalia et al / Indo J Pharm 4 (2022) 347-359
353
Until now, SLN is still being
developed as a carrier for various drugs.
One study proved that SLNs are suitable
carriers for carrying water-soluble drugs
and increase the therapeutic efficacy of
antifungal drugs, namely topical
Amphotericin B. The lipids used in this
study were Compritol® ATO 888, Precirol
ATO 5, and stearic acid, while the
surfactants or emulsifiers used were
Pluronic® F-68 and Pluronic® F-127 (44).
Nanospheres
Polymer nanoparticles are carrier
systems with a diameter of fewer than 1 m
and are divided into nanospheres or
nanocapsules based on their composition.
Nanospheres generally have smaller
diameters than nanocapsules, which are
between 10-200 nm. The nanosphere is
formed by a homogeneous solid polymer
matrix or lipid in which the active
compound will be dispersed or dissolved on
the surface, and can also be trapped in the
polymer structure. The hydrophobic
surfaces of nanospheric particles are highly
susceptible to opsonization and cleaning by
the reticuloendothelial system.
Nanospheres can be amorphous or
crystalline which can protect the drug from
enzymatic degradation. In addition, the
nanospheres can easily penetrate cells and
tissues to reach the desired target, and the
high surface reactivity of the particles
makes active targeting of the nanospheres
possible by various types of ligands (45).
The preparation of polymer
nanoparticles (nanospheres and
nanocapsules) can be carried out by various
methods. The polymerization of alkyl
cyanoacrylates in the emulsion leads to
nanoferrous matrix nanoparticles, while the
addition of organic solvents and oil in this
medium gives vesicular nanostructures,
namely nanocapsules, with interfacial
polymerization (46). The polymer
nanoparticle preparation methods can be
summarized into two approaches, namely
monomer polymerization, and polymer
dispersion. Monomer polymerization can
be carried out by emulsion polymerization
and dispersion polymerization methods.
Whereas polymer dispersion prepared by
emulsion/solvent evaporation,
nanoprecipitation, salting out, emulsion
cross-linking, coacervation, spray-drying
and spray-freezing, supercritical fluid
technology, and ionic gelation (47).
The monomer polymerization
technique works on the bottom-up principle
and allows monomer units to be
transformed into polymer carrier systems
by chemical reactions. This technique
makes it possible to obtain smaller and
monodisperse nanoparticles. In the polymer
dispersion technique, the polymerization
step is not carried out, but this technique is
based on the preparation of the existing
nanostructure system. This technique can
be carried out for the preparation of
nanostructures from natural and
biodegradable polymers that produce
nanoparticles with larger and polydisperse
sizes (47).
One of the studies using nanosphere
as DDS is the combination of Rutin and
Benzamide as an anti-cancer drug. The
preparation was carried out using a polymer
dispersion technique where PLGA
(poly(lactic-co-glycolic acid)) was first
dissolved using chloroform, then the
polymer was dispersed into PVA
(poly(vinyl alcohol)). Then sonification
and centrifugation were carried out to make
the emulsion and remove the solvent and
the dispersed pellet was compacted. Rutin
and Benzamine loaded with nanospheric
PLGA were developed using the
water/oil/water emulsion technique (48).
Nanocapsules
Nanocapsules are nanoscale shells
made of natural or synthetic polymers.
Nanocapsules consist of a characteristic
liquid/solid core in which drugs, genes,
proteins, and other substances are
introduced into the core cavity or adsorbed
on the outer surface or both. The core of the
nanosphere can effectively increase the
encapsulation efficiency of the drug while
E. Amalia et al / Indo J Pharm 4 (2022) 347-359
354
reducing the polymer matrix content of the
nanoparticles, as well as reducing tissue
irritation due to the polymer shell (49,50).
The polymer shell can be adapted by
molecules that can interact with the target
biomolecule thereby allowing for drug
delivery to a specific target (51). In
addition, the encapsulation of nanocapsules
can also slow down and prevent the
degradation process from environmental
factors (52).
The preparations of nanocapsules
that are often used are gelation, ionic, layer
by layer, interface deposition, interface
polymerization method, interface
deposition, interface deposition, self-
assembly method, nanoprecipitation
method, double emulsion-solvent
evaporation, and others. The method
chosen can be adapted to the desired
nanocapsule (53). For example, for the
encapsulation of hydrophilic drugs, the
method that can be used is double
emulsion-solvent evaporation because this
method can protect the drug from
encapsulation efficiency due to the drug
partitioning into the external aqueous phase
when using a single emulsion. This method
involves adding two surfactants to a w/o/w
emulsion with evaporation in the final step
to evaporate the solvent (54).
As for hydrophobic drugs, the
method that can be used for the preparation
of nanocapsules is interfacial deposition in
which an organic phase containing
polymers and active substances is added to
the aqueous phase. Then when the
interfacial tension decreases, the polymer
will move and form a nanocapsule
membrane, leaving the active substance in
the organic phase (51,55). One of the
formulations with an interface deposition
method based on research with the active
ingredient Dutasteride is to use polymer
films of poly-(ɛ-caprolactone) and poly-(ɛ-
caprolactone) chitosan; the Core portion
with sorbitan monostearate and
caprylic/capric triglycerides; Surfactant
with lecithin and polysorbate 80; The
organic phase of acetone and ethanol; and
inorganic phase with water (56).
Nanocapsules have been and
continue to be developed for transdermal
and dermal delivery, tumor targeting,
diabetes, antiseptic, cosmetic, anti-
inflammatory, and cancer treatment.
Research on the encapsulation of
doxorubicin in furcellaran/chitosan
nanocapsules has demonstrated the ability
of nanocapsules to enter cancer cells by
endocytosis and induce apoptosis (57).
Gold Nanoparticles
Gold nanoparticles (AuNPs/GNPs)
are small water-dispersed gold particles
with a diameter of 1 to 100 nm, also known
as colloidal gold. GNPs consist of a gold-
bearing core surrounded by a protective
outer layer of organic ligands. GNP is the
safest carrier and has low toxicity, optical,
plasmonic, and magnetic properties with a
large surface area. In addition, GNP can be
modified to be multifunctional, for example
by using a ligand-exchange reaction that
makes a single layer able to carry the active
substance. The active substance will be
attached to the GNP and can be targeted
passively or actively. In passive targeting,
GNP will enter the bloodstream and will
accumulate at the desired target site due to
permeability and retention effects. Whereas
in active targeting, GNP will be conjugated
to the ligand and the ligand will interact
with the receptor (58).
GNPs can be synthesized using
HAuCl4 reduction or other chemical
methods to obtain the desired size and
function of the ligand, for example in the
preparation of GNP fig leaf extract for the
treatment of breast cancer. HauCl4 was
obtained by dissolving by heating gold bars
in aqua regia, then aqua pro injection was
added and homogenized. Then the fig leaf
extract was added and sonicated. The result
of this research is the GNP measuring 80.46
± 0.28 (59). In addition to chemical
methods, GNP preparation can be carried
out using physical methods including
radiation, UV-irradiation, microwave
E. Amalia et al / Indo J Pharm 4 (2022) 347-359
355
irradiation, NIR irradiation, sonochemical
methods, radiolysis, and thermolysis
(58,60).
Currently, NU-0129, an injectable
nucleic acid composed on the surface of
GNPs, is in the process of phase 1 clinical
trial. This drug is used in patients with
glioblastoma multiforme or recurrent
gliosarcoma. NU-0129 acts by crossing the
blood barrier and targeting the BCL2L12
gene present in glioblastoma multiforme
(61).
3.3 Future Drug Delivery System
Development
Currently, nanoparticle drug
delivery systems have been used in the
treatment of cancer (ovarian, breast,
pancreatic), HIV, AIDS, leukemia,
osteosarcoma, liver disorders, and others.
Currently, research on DDS can be
expanded to use for other treatments, such
as drugs for diabetes, hypertension, and
wounds. Regulation of nanoparticles
should also be carried out as the
development of DDS. For example, some
drugs in clinical trials are TLC599
(Dexamethasone liposomal), OP-101
(Dendrimer N-acetyl-cysteine), NK105
(Paclitaxel micellar), and NU-0129
(Spherical Nucleic Acid in GNP) (62).
These drugs continue to be studied and
developed to treat various types of diseases,
including Covid-19.
In addition, studies of possible
adverse reactivity of nanoparticles are
lacking and conceptual understanding of
the interactions of nanoparticle
formulations themselves with cells, organs,
and living organisms is lacking. In the
development of DDSs, such understanding
is needed to minimize toxic effects and
apply safe nanoparticle materials in the
future (63).
4. Conclusion
Nanoparticle Drug Delivery
Systems (DDS) with size 1-100 nm have
exhibit advantages to be applied as
medicine for specific treatment. It able to be
designed in variation of structures and
properties to deliver active ingredients to
specific target sites so that they can increase
the therapeutic effect for the treatment. The
nanoparticle DDS able to anticipate the
shortcomings of conventional drugs
containing low solubility and
bioavailability of drug and have been useful
in the treatment of many diseases including
cancer and antifungal therapy. Therefore,
the development of nanoparticle
technology is promising to be developed
with several consideration aspects to
improve human health.
References
1. Alhara Yuwanda SSMS, Dewi
Rahmawati SFMF, apt. Rizky
Farmasita B SFMF, Indonesia MS.
Sistem Penghantaran Obat dan
Pentargetan Sediaan Nanopartikel dan
Penghantarannya. Media Sains
Indonesia; 2021.
2. Wang J, Ni Q, Wang Y, Zhang Y, He
H, Gao D, et al. Nanoscale drug
delivery systems for controllable drug
behaviors by multi-stage barrier
penetration. J Control Release.
2021;331:282–95.
3. Tewabe A, Abate A, Tamrie M, Seyfu
A, Abdela Siraj E. Targeted Drug
Delivery - From Magic Bullet to
Nanomedicine: Principles, Challenges,
and Future Perspectives. J Multidiscip
Healthc. 2021;14:1711–24.
4. Mu Y, Gong L, Peng T, Yao J, Lin Z.
Advances in pH-responsive drug
delivery systems. OpenNano.
2021;5:100031.
5. Sukmawati A, Da’i M, Zulinar F, Hanik
A. Profil Pelepasan Antikanker
kombinasi Doksorubisin dan Analog
E. Amalia et al / Indo J Pharm 4 (2022) 347-359
356
Kurkumin dari Nanopartikel Kitosan.
URECOL. 2017;139–44.
6. Saiyad M, Shah N. Nanopolymers in
drug delivery system. Mater Today
Proc. 2022;
7. Park H, Otte A, Park K. Evolution of
drug delivery systems: From 1950 to
2020 and beyond. J Control Release.
2022 Feb 1;342:53–65.
8. Yun YH, Lee BK, Park K. Controlled
Drug Delivery: Historical perspective
for the next generation. J Control
Release. 2015/10/09. 2015 Dec
10;219:2–7.
9. Kim E, Erdos G, Huang S, Kenniston
TW, Balmert SC, Carey CD, et al.
Microneedle array delivered
recombinant coronavirus vaccines:
Immunogenicity and rapid translational
development. EBioMedicine.
2020;55:102743.
10. Hryniewicz BM, Volpe J, Bach-Toledo
L, Kurpel KC, Deller AE, Soares AL, et
al. Development of polypyrrole
(nano)structures decorated with gold
nanoparticles toward immunosensing
for COVID-19 serological diagnosis.
Mater Today Chem. 2022;24:100817.
11. Rajput S, Pink D, Findlay S, Woolner
E, Lewis JD, McDermott MT.
Application of Surface-Enhanced
Raman Spectroscopy to Guide Therapy
for Advanced Prostate Cancer Patients.
ACS Sensors. 2022 Mar 25;7(3):827–
38.
12. Ramanathan S, Gopinath SCB, Arshad
MKM, Poopalan P, Perumal V. 2 -
Nanoparticle synthetic methods:
strength and limitations. In: Gopinath
SCB, Gang FBT-N in A and MD,
editors. Elsevier; 2021. p. 31–43.
13. Wang C, Piao J, Li Y, Tian X, Dong Y,
Liu D. Construction of Liposomes
Mimicking Cell Membrane Structure
through Frame-Guided Assembly.
Angew Chemie Int Ed. 2020 Aug
24;59(35):15176–80.
14. Alam MI, Paget T, Elkordy AA.
Formulation and advantages of
furazolidone in liposomal drug delivery
systems. Eur J Pharm Sci.
2016;84:139–45.
15. Zhang H. Thin-Film Hydration
Followed by Extrusion Method for
Liposome Preparation. Methods Mol
Biol. 2017;1522:17–22.
16. Ghanbarzadeh S, Valizadeh H, Zakeri-
Milani P. Application of response
surface methodology in development of
sirolimus liposomes prepared by thin
film hydration technique. Bioimpacts.
2013/04/30. 2013;3(2):75–81.
17. FDA. No Title [Internet]. [cited 2022
Jun 17]. Available from:
https://www.accessdata.fda.gov/drugsa
tfda_docs/label/2007/050718s029lbl.p
df
18. Anselmo AC, Mitragotri S.
Nanoparticles in the clinic: An update.
Bioeng Transl Med. 2019 Sep
5;4(3):e10143–e10143.
19. Rahmi D. Review Dendrimer: Definisi,
Sintesis, Aplikasi Dan Prospektif. J
Kim dan Kemasan. 2013;35(2):137–44.
20. Maingi V, Kumar MVS, Maiti PK.
PAMAM Dendrimer–Drug
Interactions: Effect of pH on the
Binding and Release Pattern. J Phys
Chem B. 2012 Apr 12;116(14):4370–6.
21. Das I, Borah JH, Sarma D, Hazarika S.
Synthesis of PAMAM dendrimer and
its derivative PAMOL: Determination
of thermophysical properties by DFT. J
Macromol Sci Part A. 2018 Jul
3;55(7):544–51.
22. Bondareva J, Rozhkov V, Kachala V V,
Fetyukhin V, Lukin O. An optimized
divergent synthesis of sulfonimide-
based dendrimers achieving the fifth
generation. Synth Commun.
2019;49(24):3536–45.
23. Gillani SS, Munawar MA, Khan KM,
Chaudhary JA. Synthesis,
characterization and applications of
poly-aliphatic amine dendrimers and
dendrons. J Iran Chem Soc.
2020;17(11):2717–36.
24. Kelly BD, McLeod V, Walker R,
Schreuders J, Jackson S, Giannis M, et
al. Abstract 1716: Anticancer activity of
E. Amalia et al / Indo J Pharm 4 (2022) 347-359
357
the taxane nanoparticles, DEP®
docetaxel and DEP® cabazitaxel.
Cancer Res. 2020 Aug
15;80(16_Supplement):1716.
25. Madaan K, Kumar S, Poonia N, Lather
V, Pandita D. Dendrimers in drug
delivery and targeting: Drug-dendrimer
interactions and toxicity issues. J Pharm
Bioallied Sci. 2014 Jul;6(3):139–50.
26. Marianecci C, Di Marzio L, Rinaldi F,
Celia C, Paolino D, Alhaique F, et al.
Niosomes from 80s to present: The state
of the art. Adv Colloid Interface Sci.
2014;205:187–206.
27. Asaithambi K, Muthukumar J,
Chandrasekaran R, Ekambaram N,
Roopan M. Synthesis and
characterization of turmeric oil loaded
non-ionic surfactant vesicles
(niosomes) and its enhanced larvicidal
activity against mosquito vectors.
Biocatal Agric Biotechnol.
2020;29:101737.
28. Ravalika V, krishna sailaja A.
Formulation and Evaluation of
Etoricoxib Niosomes by Thin Film
Hydration Technique and Ether
Injection Method. Nano Biomed Eng.
2017 Jan 1;9.
29. Javani R, Hashemi FS, Ghanbarzadeh
B, Hamishehkar H. Quercetin-loaded
niosomal nanoparticles prepared by the
thin-layer hydration method:
Formulation development, colloidal
stability, and structural properties.
LWT. 2021;141:110865.
30. Kaur D, Kumar S. Niosomes: present
scenario and future aspects. J drug
Deliv Ther. 2018;8(5):35–43.
31. Ahmed A, Ghorab M, Gad S, Qushawy
M. Design, formulation, and evaluation
of piroxicam niosomal gel. Int J
PharmTech Res. 2014 Jan 1;6:185–95.
32. Althomali NM, Alshammari RS, Al-
atawi TS, Aljohani AA. Impact of
Biocompatible Poly(ethylene glycol)-
blockPoly(ε-caprolactone) Nano-
Micelles on the Antifungal Efficacy of
Voriconazole. Biointerface Res Appl
Chem. 2022;13(1):62.
33. Ahmad Z, Shah A, Siddiq M, Kraatz H-
B. Polymeric micelles as drug delivery
vehicles. RSC Adv. 2014;4(33):17028–
38.
34. Patravale VB, Upadhaya PG, Jain RD.
Preparation and Characterization of
Micelles BT - Pharmaceutical
Nanotechnology: Basic Protocols. In:
Weissig V, Elbayoumi T, editors. New
York, NY: Springer New York; 2019.
p. 19–29.
35. Feng YH, Zhang XP, Li JY, Guo XD.
How is a micelle formed from
amphiphilic polymers in a dialysis
process: Insight from mesoscopic
studies. Chem Phys Lett.
2020;754:137711.
36. Werner ME, Cummings ND, Sethi M,
Wang EC, Sukumar R, Moore DT, et al.
Preclinical evaluation of Genexol-PM,
a nanoparticle formulation of
paclitaxel, as a novel radiosensitizer for
the treatment of non-small cell lung
cancer. Int J Radiat Oncol Biol Phys.
2013 Jul 1;86(3):463–8.
37. Jafar G, Agustin E, Puryani D.
Pengembangan formula solid lipid
nanoparticles (SLN) Hidrokortison
Asetat. J Pharmascience. 2019;6(1):83–
96.
38. Federer C, Spleis HV, Summonte S,
Friedl JD, Wibel R, Bernkop-Schnürch
A. Preparation and Evaluation of
Charge Reversal Solid Lipid
Nanoparticles. J Pharm Sci. 2022;
39. Thakkar A, Chenreddy S, Wang J,
Prabhu S. Evaluation of ibuprofen
loaded solid lipid nanoparticles and its
combination regimens for pancreatic
cancer chemoprevention. Int J Oncol.
2015;46(4):1827–34.
40. Hamishehkar H, Same S, Adibkia K,
Zarza K, Shokri J, Taghaee M, et al. A
comparative histological study on the
skin occlusion performance of a cream
made of solid lipid nanoparticles and
Vaseline. Res Pharm Sci. 2015 Oct
1;10:378–87.
41. Duan Y, Dhar A, Patel C, Khimani M,
Neogi S, Sharma P, et al. A brief review
E. Amalia et al / Indo J Pharm 4 (2022) 347-359
358
on solid lipid nanoparticles: part and
parcel of contemporary drug delivery
systems. RSC Adv.
2020;10(45):26777–91.
42. Silva AC, González-Mira E, García
ML, Egea MA, Fonseca J, Silva R, et al.
Preparation, characterization and
biocompatibility studies on risperidone-
loaded solid lipid nanoparticles (SLN):
High pressure homogenization versus
ultrasound. Colloids Surfaces B
Biointerfaces. 2011;86(1):158–65.
43. Li Y, Dong L, Jia A, Chang X, Xue H.
Preparation of solid lipid nanoparticles
loaded with traditional Chinese
medicine by high-pressure
homogenization. Nan Fang Yi Ke Da
Xue Xue Bao. 2006 May;26(5):541–4.
44. Butani D, Yewale C, Misra A. Topical
Amphotericin B solid lipid
nanoparticles: Design and
development. Colloids Surf B
Biointerfaces. 2016 Mar;139:17–24.
45. Singh AK, Garg G, Sharma PK.
NANOSPHERES: A NOVEL
APPROACH FOR TARGETED
DRUG DELIVERY SYSTEM. In
2010.
46. Guterres SS, Alves MP, Pohlmann AR.
Polymeric nanoparticles, nanospheres
and nanocapsules, for cutaneous
applications. Drug Target Insights.
2007/07/11. 2007;2:147–57.
47. Pippa N, Demetzos C, Pispas S. Drug
Delivery Nanosystems: From
Bioinspiration and Biomimetics to
Clinical Applications. Jenny Stanford
Publishing; 2019.
48. Deepika MS, Thangam R, Sheena TS,
Vimala RT V, Sivasubramanian S,
Jeganathan K, et al. Dual drug loaded
PLGA nanospheres for synergistic
efficacy in breast cancer therapy. Mater
Sci Eng C. 2019;103:109716.
49. Szczepanowicz K, Piechota P, Węglarz
WP, Warszyński P. Polyelectrolyte
nanocapsules containing iron oxide
nanoparticles as MRI detectable drug
delivery system. Colloids Surfaces A
Physicochem Eng Asp. 2017;532:351–
6.
50. Yang WJ, Zhao T, Zhou P, Chen S, Gao
Y, Liang L, et al. “Click”
functionalization of dual stimuli-
responsive polymer nanocapsules for
drug delivery systems11Electronic
supplementary information (ESI)
available. See DOI:
10.1039/c7py00161d. Polym Chem.
2017;8(20):3056–65.
51. Trindade IC, Pound-Lana G, Pereira
DGS, de Oliveira LAM, Andrade MS,
Vilela JMC, et al. Mechanisms of
interaction of biodegradable polyester
nanocapsules with non-phagocytic
cells. Eur J Pharm Sci. 2018;124:89–
104.
52. Yunessnia lehi A, Shagholani H,
Ghorbani M, Nikpay A, Soleimani
lashkenari M, Soltani M. Chitosan
nanocapsule-mounted cellulose
nanofibrils as nanoships for smart drug
delivery systems and treatment of avian
trichomoniasis. J Taiwan Inst Chem
Eng. 2019;95:290–9.
53. Setianty TN, Priani SE, Aryani R.
Kajian Metode Pembuatan dan Bahan
Penyalut pada Formulasi Nanokapsul
Agen Sitotoksik. Pros Farm. 2021;190–
7.
54. Shirode AB, Bharali DJ, Nallanthighal
S, Coon JK, Mousa SA, Reliene R.
Nanoencapsulation of pomegranate
bioactive compounds for breast cancer
chemoprevention. Int J Nanomedicine.
2015;10:475–84.
55. Buss JH, Begnini KR, Bruinsmann FA,
Ceolin T, Sonego MS, Pohlmann AR, et
al. Lapatinib-Loaded Nanocapsules
Enhances Antitumoral Effect in Human
Bladder Cancer Cell. Front Oncol. 2019
Apr 9;9:203.
56. Ushirobira C, Afiune L, Pereira M,
Cunha Filho M, Gelfuso G, Gratieri T.
Dutasteride nanocapsules for hair
follicle targeting: Effect of chitosan-
coating and physical stimulus. Int J Biol
Macromol. 2020 Feb 1;151.
E. Amalia et al / Indo J Pharm 4 (2022) 80-92
359
57. Milosavljevic V, Jamroz E, Gagic M,
Haddad Y, Michalkova H, Balkova R,
et al. Encapsulation of Doxorubicin in
Furcellaran/Chitosan Nanocapsules by
Layer-by-Layer Technique for
Selectively Controlled Drug Delivery.
Biomacromolecules. 2020;21(2):418–
34.
58. Yafout M, Ousaid A, Khayati Y, El
Otmani IS. Gold nanoparticles as a drug
delivery system for standard
chemotherapeutics: A new lead for
targeted pharmacological cancer
treatments. Sci African.
2021;11:e00685.
59. Syukri Y, Nugroho BH, Febriana Y,
Ningrum ADK, Maharani GA.
INOVASI PENGOBATAN
ANTIKANKER PAYUDARA DARI
NANOPARTIKEL EMAS EKSTRAK
DAUN TIN (Ficus carica L.).
Khazanah J Mhs. 2020 Sep 5;11(1 SE-
Articles).
60. Hussain MH, Abu Bakar NF, Mustapa
AN, Low K-F, Othman NH, Adam F.
Synthesis of Various Size Gold
Nanoparticles by Chemical Reduction
Method with Different Solvent Polarity.
Nanoscale Res Lett. 2020;15(1):140.
61. NIH. No NU-0129 in Treating Patients
With Recurrent Glioblastoma or
Gliosarcoma Undergoing SurgeryTitle
[Internet]. 2020 [cited 2022 Jun 23].
Available from:
https://www.clinicaltrials.gov/ct2/show
/NCT03020017
62. nih. ClinicalTrial.gov [Internet]. 2022
[cited 2022 Jul 15]. Available from:
https://clinicaltrials.gov/
63. De Jong WH, Borm PJA. Drug delivery
and nanoparticles:applications and
hazards. Int J Nanomedicine.
2008;3(2):133–49.

Refbacks

  • There are currently no refbacks.