Introduction
The chemotherapy for the brain cancer treatment is very
difficult due to the presence of blood–brain barrier (BBB) and
blood–tumor barrier (BTB) (Van et al., 2015; Fortin, 2012).
BBB consist of the endothelial cells, joined together by tight
junctions by which transport of most of the drugs from the blood
into the brain is hampered. The luminal side of the BBB also
contains efflux membrane transporters like P-glycoprotein
(Pgp) and multidrug resistance related proteins which recognize
the anticancer drugs as substrates (Löscher and Potschka, 2005).
BBB and BTB limit the amount of drugs that can be delivered to
the tumor site. It causes insufficiency of drug at the target site to
achieve a therapeutic concentration. Hence, there is a need to
employ a strategy which can deliver the cytotoxic drug to the
brain at the therapeutic level. Ligand conjugated nano carrier
bearing drug capable of recognizing the brain capillary
endothelial cells and brain cancer cells have shown promising
potential in brain cancer treatment ( . Pinto et al., 2017)
Among the various ligands, transferrin was selected for
targeting to the BBB as well as brain cancer cells. Transferrin is
an endogenous glycoprotein which transports iron through
transferrin receptor (TR) (Kang et al., 2015 . TR are selectively )
expressed on the luminal membrane of brain endothelial cells
and also on the brain cancer cells ( Trowbridge Li et al., 2016,
and Omary, 1981). Therefore, TfR were used to increase the
uptake of SLN across the brain endothelial cells and also in
brain tumor cells (Choudhury et al., 2018, Yang et al., 2008).
SLN are the most promising carrier for the brain delivery of
cytotoxic drugs due to its biocompatibility and biodegradability
(Soni et al., 2017; Shankar et al., 2018). Doxorubicin (DOX) is
a cytotoxic drug belongs to anthracycline class, shows a wide
antitumor spectrum (Cagel et al., 2017, Cutts et al., 2005).
DOX stop the cell cycle by intercalating between paired bases
of DNA. DOX also prevent the topoisomerase II mediated
DNA repair (Yang et al., 2014; Thorn et al., 2011). The
resistance for DOX causes reduction in drug binding to DNA of
cancer cells due to efflux mechanism occurs through P-
glycoproteins (Ling 1992). The DOX also causes the
cardiotoxicity and therefore to avoid its distribution in normal
cells, direct targeting to cancer cells is important.
Keeping also these facts in mind in the present research work,
transferrin was used as ligand anchored on the surface of SLN
bearing doxorubicin.
Transferrin anchored solid lipid nanoparticles for brain cancer treatment
Priyanka Jain,Vandana Soni*
Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar 470 003, Madhya Pradesh, India.
* Corresponding Author: Address for
Prof. VandanaSoni,
Department of Pharmaceutical Sciences,
Dr.Hari Singh Gour, Central University, Sagar, Madhya Pradesh, 470
003, India.
Email: drvandanasoni@gmail.com
Abstract
Objective: The aim of this study was to investigate the targeting potential of transferrin anchored solid lipid
nanoparticles (SLN) loaded with doxorubicin (D-SLN-T). Transferrin receptors (TR) are Material and methods:
highly expressed on blood brain barrier as well as brain cancer cells. Therefore, targeting TR using transferrin (Tf)
improved the anticancer activity of prepared nanoparticles. The Tf coupled SLN were characterized by fourier
transform infrared spectroscopy, transmission electron microscopy, particle size, particle size distribution, zeta
potential, % entrapment efficiency, vitro drug release and cell line studies. The average Results and conclusion:
particle size of the D-SLN-T was found to be 210.3±1.3 nm with a negative surface charge. The cell line studies, on U87
MG brain cancer cell lines, showed that the cytotoxicity of D-SLN-T was highly increased when anchored with
transferrin. Also, the presence of transferrin on the surface of the D-SLN-T enhanced the cellular uptake of drug on
U87MG cell line. The results of the cytotoxicity and cellular uptake studies clearly showed the potential of D-SLN-T in
brain cancer treatment.
Keywords: Transferrin, brain, solid lipid nanoparticles, doxorubicin, drug delivery
Received: 18 January 2019 Revised: 11 March 2019 Accepted: 17 March 2019
Research Article
www.ajpp.in
DOI: https://doi.org/10.31024/ajpp.2019.5.5.10
2455-2674/Copyright © 2019, N.S. Memorial Scientific Research and Education Society. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
Asian Journal of Pharmacy and Pharmacology 2019; 5(5):922-928 922