Cytocompatible chitosan-graft-mPEG-based 5-fluorouracil-loaded polymeric nanoparticles for tumor-targeted drug delivery

Abstract

Biodegradable materials like chitosan (CH) and methoxy polyethylene glycol (mPEG) are widely being used as drug delivery carriers for various therapeutic applications. In this study, copolymer (CH-g-mPEG) of CH and carboxylic acid terminated mPEG was synthesized by carbodiimide-mediated acid amine reaction. The resultant hydrophilic copolymer was characterized by Fourier transform infrared spectroscopy and ¹H NMR studies, revealing its relevant functional bands and proton peaks, respectively. Blank polymeric nanoparticles (B-PNPs) and 5-fluorouracil loaded polymeric nanoparticles (5-FU-PNPs) were formulated by ionic gelation method. Furthermore, folic acid functionalized FA-PNPs and FA-5-FU-PNPs were prepared for folate receptor-targeted drug delivery. FA-5-FU-PNPs were characterized by particle size, zeta potential, and in vitro drug release studies, resulting in 197.7 nm, +29.9 mv, and sustained drug release of 88% in 24 h, respectively. Cytotoxicity studies were performed for FA-PNPs and FA-5-FU-PNPs in MCF-7 cell line, which exhibited a cell viability of 80 and 41%, respectively. In vitro internalization studies were carried out for 5-FU-PNPs and FA-5-FU-PNPs which demonstrated increased cellular uptake of FA-5-FU-PNPs by receptor-mediated transport. Significant (p < .01) reduction (1.5-fold) of reactive oxygen species (ROS) accumulation was observed in lipopolysaccharides-stimulated RAW264.7 macrophages, revealing its potent antioxidant property. From the obtained results, it is concluded that folic acid functionalization of 5-FU-PNPs is an ideal approach for sustained and targeted drug delivery, thereby influencing better therapeutic effect.

Keywords:

• Chitosan-g-mPEG
• mPEG-carboxylic acid
• biocompatibility
• polymer synthesis
• polymeric nanoparticles
• MTT assay
• hemolysis
• folic acid
• targeted drug delivery

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by Nanomission program of the Department of Science and Technology (DST), Ministry of Science and Technology of India (DST/SR/NM/NS-19/2009). We also wish to acknowledge the DST sponsored National Facility for Drug Development (VI-D&P/349/10-11/TDT/1), University Grants Commission (UGC) sponsored Maulana Azad national Fellowship for Minority Students (F1-17.1/2013-14/MANF-2013-14-CHR-TAM-25389) and Technical Education Quality Improvement rogramme (TEQIP) for their partial support in this work.