Abstract

Ferulic acid (FA) is a widely distributed hydroxycinnamic acid found in various cereals and fruits exhibiting potent antioxidant and anticancer activities. However, due to low solubility and permeability, its availability to biological systems is limited. Non-toxic chitosan-tripolyphosphate pentasodium (CS-TPP) nanoparticles (NPs) are used to load sparingly soluble molecules and drugs, increasing their bioavailability. In the present work, we have encapsulated FA into the CS-TPP NPs to increase its potential as a therapeutic agent. Different concentrations of FA were tested to obtain optimum sized FA-loaded CS-TPP nanoparticles (FA/CS-TPP NPs) by ionic gelation method. Nanoparticles were characterized by scanning electron microscopy, Fourier transformation infrared spectroscopy (FTIR), thermogravimetric analyses and evaluated for their anticancer activity against ME-180 human cervical cancer cell lines. The FTIR spectra confirmed the encapsulation of FA and thermal analysis depicted its degradation profile. A concentration-dependent relationship between FA encapsulation efficiency and FA/CS-TPP NPs diameter was observed. Smooth and spherical FA-loaded cytocompatible nanoparticles with an average diameter of 125 nm were obtained at 40 µM FA conc. The cytotoxicity of 40 µM FA/CS-TPP NPs against ME-180 cervical cancer cell lines was found to be higher as compared to 40 µM native FA. Apoptotic morphological changes as cytoplasmic remnants and damaged wrinkled cells in ME-180 cells were visualized using scanning electron microscopic and fluorescent microscopic techniques. Data concluded that chitosan enveloped FA nanoparticles could be exploited as an excellent therapeutic drug against cancer cells proliferation.

Highlights

  • Ferulic acid (FA) (4-hydroxy-3-methoxycinnamic acid) is the most abundant hydroxycinnamic acid found in plant cell walls forming covalent ester linkages to polysaccharides and ether or ester linkages to lignin

  • Human cervical cancer ME-180 and Human Embryonic Kidney (HEK-293) cell lines obtained from National Centre for Cell Science (NCCS), Pune, India were used in this study

  • FA ferulic acid, NPs nanoparticles, EE encapsulation efficiency, LC loading capacity, FA/CS-TPP ferulic acid-loaded chitosan-tripolyphosphate pentasodium, Avg average, Dia diameter selected for the preparation of FA-loaded nanoparticles

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Summary

Introduction

Ferulic acid (FA) (4-hydroxy-3-methoxycinnamic acid) is the most abundant hydroxycinnamic acid found in plant cell walls forming covalent ester linkages to polysaccharides and ether or ester linkages to lignin. The strong antioxidant character of FA is attributed to its unsaturated side chain and phenolic nucleus that spontaneously forms resonance stabilized structures, making it an effective antiproliferative agent. Radiotherapy is the major therapeutic technique to minimize the effect of cervical cancer but due to its adverse effect on normal tissues, alternative plant-derived therapeutic drugs are being tested increasingly (Seiwert et al 2007). A large number of natural compounds have shown cytotoxic effects in different cancer models either alone or together with radiation (Garg et al 2005). Effects of FA on human cervical carcinoma cells ME-180 and HeLa have been studied and indicated that FA treatment significantly decreased radiation surviving fraction of the cancer cells and increased the lipid peroxidation indices (Subburayan et al 2011)

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