Article Review
Nanoparticles targeted drug delivery system via epidermal growth factor receptor : a review
Agus Rusdin1, Nasrul Wathoni1,*, Keiichi Motoyama4, I Made Joni2, Ronny Lesmana5, Muchtaridi2
1
Department of Pharmaceutics, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, Indonesia,
45363
2
Department of Physics, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran,
Sumedang, Indonesia, 45363
3
Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas
Padjadjaran, Sumedang, Indonesia, 45363
4
Department of Pharmacy, Faculty of Sports and Health, Universitas Negeri Gorontalo, Gorontalo,
Indonesia, 96128
5
Department of Anatomy, Physiology and Biology Cell, Faculty of Medicine, Universitas Padjadjaran,
Sumedang, Indonesia, 45363
*Corresponding author: email address: nasrul@unpad.ac.id
Abstract
Over expressing of epidermal growth factor receptor (EGFR) in specific organ implicates a tumor
aggression and proliferation. Therefore, EGFR becomes a basic consideration for targeted cancer
therapy. Nanoparticle drug delivery system is a promising multifunctional technique to provide the
targeted drug delivery system. This review aimed to discuss about the nanoparticles formulation for
targeted drug delivery in specifics EGFR. The data were collected from published journals recorded in
the scopus data base since 2017 to present. A various types of nanoparticles are widely studied to
provide an EGFR-targeted drug delivery system. It was formulated using a specific targeted mediators
were conjugated on several types of nanoparticle formulations such as polymeric nanoparticles,
nanometals, liposomes, nanobiomaterials and micellanous nanoparticles. Impressive results were
shown from Superparamagnetic iron oxide nanoparticles with EGF conjugates, it can mediate targeted
delivery across the blood-brain barrier and tumor retention of the nanoparticles, and the accumulation
revealed as hypotensive zones on T2-weighted images with a twofold reduction in T2 relaxation time
compare to unconjugates. EGRF-targeted drug delivery system could be a promising technique to
provide a high effectiveness of drugs in EGFR-positive cells cancers with a lower side effects to non
tumor cells.
Key words: Epidermal growth factor receptor, Cancers, Nanoparticle drug delivery
1. Introduction
2. methodology
3. Nanoparticles drug delivery system
4. Epidermal growth factor receptor (EGFR)
5. Nanoparticles formulation as EGFR-targeted drug delivery system
5.1. Polymeric based nanoparticle for EGRF-targeted drug delivery system
5.1.1 Biopolymer based
5.1.1 Synthetic polymer based
5.2. Metal based nanoparticle for EGFR-targeted drug delivery system
5.2.1 Gold based nanoparticle
5.2.2 Cu based nanoparticle
5.3.3 Fe3O4 based nanoparticle
5.3. Liposome based nanoparticle for EGFR-targeted drug delivery system
5.4. Biomaterial based nanoparticle for EGFR-targeted drug delivery system
6. Perspective Author
7. Conclusion
1. Introduction
Epidermal growth factor receptor (EGFR) is one of the human epidermal receptor (HER1) where
include in family of receptor tyrosine kinases. The receptor was consist of a single chain transmembran
of glycoprotein an extracellular ligan-binding domain, it was also a transmembrane region an
intercellular tyrosine kinase domain1,2. The EGFR has a multifunctional and responsible for several
cell regulations such as proliferation, growth, differentiation and programmed cell death (Apoptosis).
In the other hand, EGFR was play an important role in cancer cells progression, formation, metastasis
and angiogenesis
3–5
. It also has been proved becomes a specific characteristic of several cancer cells
which is indicated by EGFR over expressed on surface cells membrane, these cells are known as a
(EGFR-positive cells) which is includes of breast cancer cells, colorectal, pancreatic, colon,
glioblastoma, gastroesophageal, nasopharyngeal, bladder, ovarian, lung cancer, non small cell lung
cancer (NSCLC), head and neck squamose cancer
6,7,16,8–15
. Therefore, EGFR becomes a primary
consideration for drug targeted in clinical treatmen of cancer diseases. In previous studies, EGFR
targeted drug delivery system have been provided by many approaches include anti-cancer drugs
combination theraphy with targeting mediators till modification or complex formulation mediated by
nanoparticle targeted drug delivery system.
In last decade, nanoparticle drug delivery systems becomes an excellent technical modification
approaches were most commonly studied for development of diseases treatmen. Its multifunctional
capabilities were achieved by its nanosize and complex formulation, may becomes a fundamental
reason of this system to resolve a physicochemical problem drug performance such as solubility
problem, penetration rate and bioavalability. Its also can provide release controlled and targeted
delivery in specific cell or organ, which leads for anti-cancer drug delivery
17–19
. In addition, as we
know that the primary problem of anti cancer drugs generally has a poor site selectivity which causes a
side effect to non cancer cell20, therefore a nanoparticle targeted drug delivery system being an
alternatively technique to resolve this site selectivity problem. Many studies of nanoparticle targeted
drug delivery system have been proved effectively as a delivery carrier onto gene targeting, enzyme
and receptor like an EGFR targeted drug delivery system.
Since in 2003 to present, there is about 83 review of EGRF targeted drug delivery system were
have been published and recorded in Scopus data base. However, it is limited to discus about its
therapy agents (single/combination), strategies, resistence, pharmacogenomics, mechanism, detection
methods of EGFR mutations and there is no study is focussing on EGRF targeted mediated by
nanoparticle formulation 21–25. Therefore, we are inspired to summarize and discuss about nanoparticle
formulations for EGFR targeted drug delivery system, related on types of nanoparticle, carrier bases
and its targeting mediators. We belive that our review will be an excellent studies and basic
conderation for next development for targeted therapies of EGFR mediated nanoparticle targeted drug
delivery system.
2. Methodology
This study is based on the literatures were obtained from Scopus data base by using a specific
keywords "EGFR, targeted and nanoparticles", by following an inclusions criteria (journals were
published since 2017 to present) and exclusions criterias (opinions, reviews and unrelated topics).
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