Journal
CARBOHYDRATE POLYMERS
Volume 274, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2021.118617
Keywords
Lung cancer; Dual-targeting; EGFR; Cetuximab; Folate; Docetaxel; TPGS; Chitosan nanoparticles
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Funding
- Indian Institute of Technology-Banaras Hindu University (IIT-BHU), Varanasi, India [IIT(BHU)/R&D/IRP/2017-18/4792/L]
- Ministry of Education (Government of India)
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By successfully conjugating folate and cetuximab to chitosan nanoparticles, the cytotoxicity against A-549 cells was enhanced, and the relative bioavailability of DXL in rats was improved.
The chitosan-folate conjugate was synthesized initially and confirmed by FTIR and NMR spectroscopic studies. Following, docetaxel (DXL) loaded non-targeted, single receptor and dual receptor (folate and EGFR) targeted chitosan nanoparticles were prepared and their shape, particle size, zeta-potential, surface morphology and texture were screened by SEM, TEM, AFM analyses. Surface chemistry analysis by XPS indeed confirmed the successful conjugation of folate and cetuximab on the targeted formulations. In-vitro analysis of dual-targeted chitosan nanoparticles has revealed their superior cytotoxicity against A-549 cells. The IC50 of dual receptortargeted chitosan NP was almost 34 times lower than DXL control. In-vivo pharmacokinetic study on Wistar rats has demonstrated improved relative bioavailability of all NP in comparison to DXL control. The results illustrated that EGFR and folate dual targeted NP enhanced the cytotoxicity of DXL towards A-549 lung cancer cells and substantially improved DXL pharmacokinetics in rats.
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