期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
卷 98, 期 -, 页码 810-819出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijbiomac.2017.02.030
关键词
Chitosan; Paclitaxel; Nanoparticles; Nano-emulsion; Biodegradable polymers
资金
- Department of Science and Technology
- University Grants Commission, New Delhi, India
Taxanes have established and proven effectivity against different types of cancers; in particular breast cancers. However, the high hemolytic toxicity and hydrophobic nature of paclitaxel and docetaxel have always posed challenges to achieve safe and effective delivery. Use of bio-degradable materials with an added advantage of nanotechnology could possibly improve the condition so as to achieve better and safe delivery. In the present study paclitaxel loaded chitosan nanoparticles were formulated and optimized using simple w/o nanoemulsion technique. The observed average size, pdi, zeta potential, entrapment efficiency and drug loading for the optimized paclitaxel loaded chitosan nanopartide formulation (PTX-CS-NP-10) was 226.7 +/- 0.70 nm, 0.345 +/- 0.039, 37.4 +/- 0.77 mV, 79.24 +/- 2.95% and 11.57 +/- 0.81%; respectively. Nanoparticles were characterized further for size by Transmission Electron Microscopy (TEM). In vitro release studies exhibited sustained release pattern and more than 60% release was observed within 24 h. Enhanced in vitro anticancer activity was observed as a result of MIT assay against triple negative MDA-MB-231 breast cancer cell lines. The observed IC50 values obtained for PTX-CS-NP-10 was 9.36 +/- 1.13 mu M and was almost 1.6 folds (p <0.05) less than the pure drug. Similarly, PTX-CS-NP-10 were extremely biocompatible and safe as observed for haemolytic toxicity which was almost 4 folds less (p <0.05) than the naive drug. Anticancer activity was further evaluated using flow cytometry for apoptosis. Cell apoptosis study revealed that PTX-CS-NP-10 treatment resulted into enhanced (almost double) late cell apoptosis than naive paclitaxel. Hence the developed nanoparticulate formulation not only reduced the overall toxicity but also resulted into improved anticancer efficacy of paclitaxel. It can be concluded that a robust, stable and comparatively safe nanoformulation of paclitaxel was developed, characterized and evaluated. (C) 2017 Elsevier B.V. All rights reserved.
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