Short communicationDoxorubicin-loaded pH-responsive chitin nanogels for drug delivery to cancer cells
Highlights
► We developed doxorubicin loaded pH responsive chitin nanogels (Dox-CNGs) for cancer drug delivery applications. ► The in vitro cytotoxicity studies of 130–160 nm sized Dox-CNGs proved their cyto compatibility with L929 and toxicity towards PC3, MCF-7, A549 and HEPG2 cancer cells. ► The internalization of the Dox-CNGs showed a significant uptake of the Dox-CNGs in all the tested cell lines. ► These results indicated that Dox-CNGs can be used for prostate, breast, lung and liver cancer.
Introduction
Chitin, composed of (1–4) linked units of N-acetyl-β-d-glucosamine (some of which deacetylated), exists in the form of nanostructures in living organisms (Muzzarelli, 2011a). It is being used in the fabrication of a variety of medical devices, and regenerative medical components, thanks to its high crystallinity, biochemical significance and biocompatibility (Yimin, Tsuguyuki, & Akira, 2008). The inherent and unique properties of large and active surface area are being explored in the fields of engineering, technology and medicine (Muzzarelli, 2011b). Nanohydrogels (nanogels) are cross-linked nanoparticles made of flexible hydrophilic polymers. They swell in water and allow spontaneous loading of drugs in aqueous media (Raemdonck, Joseph, & De Smedt, 2009). They can be thus made responsive to stimuli and to changes in the environment, such as pH and temperature. Different approaches have been running in the current era to cure the cancer through encapsulating different anticancer drugs in polymeric nanomaterials. The advanced cancer treatments in terms of developing smart carrier molecules and delivering them at specific site are required treating metastatic cancers. Thus the main objective of our work is to study the efficiency of these doxorubicin loaded chitin nanogels in the controlled delivery of the doxorubicin and to analyze their cytotoxicity against the cancer cell lines in vitro.
Section snippets
Materials
Chitin (degree of acetylation – 72.4% and 150 kDa) from Koyo chemical Co., Ltd., Japan, CaCl2 and methanol from Qualigens, India. Doxorubicin from AIMS, Kochi. Cell lines from National Center for Cell Sciences, Pune, India.
Preparation of chitin nanogels and doxorubicin loaded chitin nanogels
Chitin nanogels were prepared according to our previous method (Sanoj Rejinold, Amrita Nair, et al., 2012 Sanoj Rejinold, Chennazhi, Tamura, Nair, & Jayakumar, 2011). To prepare doxorubicin loaded chitin nanogels, where the weight of doxorubicin is 10% of the weight of chitin
Preparation and characterization of doxorubicin loaded chitin nanogels
A required volume of doxorubicin was aspirated to the prepared chitin nanogels and kept for 5 h stirring. The longer the incubation is enhancing the higher loading of the drug. However the size of the nanogel was affected as before because of the surface adsorption of the drug.
The size distribution for the prepared nanogels was found to be 50–80 nm (Sanoj Rejinold et al., 2012) and 130–160 nm for the doxorubicin loaded chitin nanogels (Fig. 1A). The SEM images also confirmed the same size range
Conclusion
The biodegradable and biocompatible doxorubicin loaded chitin nanogels (130–160 nm) was prepared and characterized for cancer drug delivery applications. The doxorubicin loaded chitin nanogels showed pH sensitive controlled release of doxorubicin. Cytotoxicity studies showed that doxorubicin loaded chitin nanogels are toxic to all tested cancer cells sparing normal L929 cells. The cell uptake studies reveal that doxorubicin loaded chitin nanogels could enter and illuminate the cells for imaging
Acknowledgments
The Department of Biotechnology, Government of India supported this work, under a center grant of the Nanoscience and Nanotechnology Initiative program (Ref. No. BT/PR10850/NNT/28/127/2008). This work is also partly supported by Department of Science and Technology under the Nanoinitiative programme. The authors, N. Sanoj Rejinold and S. Maya acknowledge Council of Scientific and Industrial Research (CSIR) for the financial support through Senior Research Fellowships (N. Sanoj Rejinold; SRF;
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These authors contributed equally to this work.