Research ArticleApigenin loaded nanoparticle delayed development of hepatocellular carcinoma in rats
Graphical Abstract
Apigenin loaded PLGA nanoparticles successfully delayed hepatocellular carcinoma both in-vitro and in-vivo. Such strategic formulation of apigenin improved its bioavailability and made it more tumor site specific in nature. Again, various pharmacokinetic parameters and biodistribution of apigenin in mice plasma and liver were measured using LC-MS/MS and radiolabeling study. This study may help us to promote the usage of nanoformulations of dietary flavonoids such as apigenin in combating HCC along with the other medicines available in market.
Section snippets
Materials
Apigenin (4′, 5, 7-trihydroxyflavone, M.W 270.24) and PLGA {MW 50,000-75,000; poly (lactide-co-glycolide) ratio 85:15} were procured from Sigma-Aldrich Co, St Louis, MO, USA. Polyvinyl alcohol was purchased from S D Fine-Chemicals limited, Mumbai, India. Fluorescein isothiocyanate 98% (FITC) was purchased from HiMedia Laboratories, Mumbai, India. Dimethylsulfoxide (DMSO) and dicholoromethane (DCM) were procured from Merck Life Science Pvt. Ltd, Bengaluru, India. All other chemicals used in this
Fourier-transform infrared spectroscopy (FTIR) study
Presence of the characteristic peaks of apigenin [at wave number 1243 cm−1, responsible for C-C (O) –C stretching], PLGA (at wave number 2948 cm−1, responsible for –OH stretching) and PVA (at wave number 3426 cm−1, responsible for –OH stretching) in their physical mixture suggests that no chemical interaction took place between the drug and the excipients. However, absence of the characteristic peak of apigenin (at wave number 1243 cm−1) in apigenin loaded nanoparticles (Supplementary Figure 2)
Discussion
In recent times apigenin has gained much popularity as a naturally occurring flavonoid which has much lower intrinsic toxicity on normal cells compared to cancer cells while used as a tumor-suppressive agent.37 There are very few reports published to date, which showed tumor suppressive effect of apigenin against HCC in-vivo.14, 38, 39, 40 All these studies indicated a much higher dosing of apigenin required to acquire the therapeutic activity. To the best of our knowledge, this is the first
References (50)
- et al.
How grim is hepatocellular carcinoma?
Ann Med Surg
(2014) - et al.
Surgical treatment of hepatocellular carcinoma: expert consensus statement
HPB
(2010) - et al.
Strategic formulation of apigenin-loaded plga nanoparticles for intracellular trafficking, DNA targeting and improved therapeutic effects in skin melanoma in vitro
Toxicol Lett
(2013) - et al.
Anti-proliferative effect of apigenin and its apoptotic induction in human hep g2 cells
Cancer Lett
(2006) - et al.
Apigenin inhibits hepatoma cell growth through alteration of gene expression patterns
Phytomedicine
(2011) - et al.
Preferential hepatic uptake of paclitaxel-loaded poly-(D-L-lactide-co-glycolide) nanoparticles — a possibility for hepatic drug targeting: Pharmacokinetics and biodistribution
Int J Biol Macromol
(2018) - et al.
The carbon monoxide-binding pigment of liver microsomes. I. Evidence for its hemoprotein nature
J Biol Chem
(1964) - et al.
Sub-toxic dose of apigenin sensitizes HepG2 cells to TRAIL through ERK-dependent up-regulation of TRAIL receptor DR5
Mol Cells
(2013) - et al.
A mechanism of apigenin-induced apoptosis is potentially related to anti-angiogenesis and anti-migration in human hepatocellular carcinoma cells
Food Chem Toxicol
(2011) - et al.
Type II ground-glass hepatocytes as a marker of hepatocellular carcinoma in chronic hepatitis B
Hum Pathol
(2013)
Poor prognosis for hepatocellular carcinoma with transarterial chemoembolization pre-transplantation: retrospective analysis
World J Gastroenterol
Global cancer statistics, 2012
CA Cancer J Clin
The etiology of hepatocellular carcinoma and consequences for treatment
Oncologist
Nutrition and metabolism in hepatocellular carcinoma
Hepatobiliary Surg Nutr
Sorafenib-induced liver failure: a case report and review of the literature
Case Rep Hepatol
Dietary natural products for prevention and treatment of liver cancer
Nutrients
Role of apigenin in cancer prevention via the induction of apoptosis and autophagy
J Cancer Prev
Review of natural compounds for potential skin cancer treatment
Molecules
Apigenin inhibits nf-κb and snail signaling, emt and metastasis in human hepatocellular carcinoma
Oncotarget
Apigenin induces cell cycle arrest and p21/waf1 expression in a p53-independent pathway
Int J Oncol
Apigenin and its impact on gastrointestinal cancers
Mol Nutr Food Res
Binding citrus flavanones to human serum albumin: effect of structure on affinity
Mol Biol Rep
Pharmacokinetics and metabolism of apigenin in female and male rats after a single oral administration
Drug Metab Dispos
Pulmonary delivery of voriconazole loaded nanoparticles providing a prolonged drug level in lungs: a promise for treating fungal infection
Mol Pharm
PLGA-based nanoparticles as cancer drug delivery systems
Asian Pac J Cancer Prev
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Funding Source: This work was supported by Department of Science and Technology (Government of India), Grant no. DST/Inspire Fellowship/2012/691.
Disclosure: The authors of this article have no conflicts of interest to declare.