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

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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.

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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

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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

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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

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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).

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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

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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

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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.

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