HYALURONIC ACID-DOCETAXEL CONJUGATE LOADED NANOLIPOSOMES FOR TARGETING TUMOR CELLS
Objective: Docetaxel, a potent anticancer drug, is suffering from non-specificity and drug resistance as major limitations. In this investigation we developed Hyaluronic acid-Docetaxel conjugate (HA-DTX) loaded nanoliposomes to target cancer cells via passive and active targeting approaches.
Methods: HA-DTX was synthesized and characterized by UV-Visible spectrophotometry, FT-IR spectroscopy, 1H NMR spectroscopy, Differential scanning calorimetry and X-ray diffraction and then loaded into nanoliposomes (L-NLs) by thin film hydration method. L-NLs were characterized physicochemically and evaluated for anticancer efficacy by in vitro cytotoxicity study in glioma cells (C6 glial cells); cellular uptake and apoptotic effect were investigated by fluorescence microscopy.
Results: HA-DTX was successfully synthesized; L-NLs had an average size of 123.0±16.53 nm, polydispersity index of 0.246 and zeta potential of 44.4±6.79 mV. Also, L-NLs exhibited 90.54%±4.22 of drug loading efficiency and 2.68%±0.12 of drug loading releasing about 57.72%±1.17 at pH 5.2 and only 14.14%±1.32 at pH 7.4 after 48 h. No significant change in stability was observed after storage at 5 oC ± 3 oC as well as at 25 °C ± 2 °C/60% RH ± 5% RH for six months. The cytotoxicity effect of L-NLs was 10% higher than that of marketed formulation (percent cell viability: 15.69%±0.72 and 26.50%±0.35, respectively) at 10 µg/ml docetaxel concentration. Fluorescence microscopic investigation showed more cellular uptake and apoptotic effect were observed in L-NLs treated C6 glial cells than those treated with marketed formulation.
Conclusion: HA-DTX loaded nanoliposomes enabled docetaxel to target C6 glial cells with better efficacy and might be effective to treat glioma.
Keywords: Anticancer drug, Hyaluronic acid-Docetaxel conjugate, nanoliposomes, passive and active targeting, C6 glial cells
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