Journal
JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 105, Issue 9, Pages 2815-2824Publisher
WILEY-BLACKWELL
DOI: 10.1016/j.xphs.2016.03.031
Keywords
carbon nanotubes; peptides; pegylation; complexation; dispersion; drug delivery systems
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Single-walled carbon nanotubes (SWCNTs) attract great interest in biomedical applications including drug and gene delivery. In this study, we developed a novel delivery system using SWCNTs associated with designed polycationic and amphiphilic peptides. Wrapping of SWCNTs with H-(-Lys-Trp-Lys-Gly-)(7)-OH [(KWKG)(7)] resulted in stable dispersion in water, but the composite aggregated in the buffered solution. This dispersion instability was also evident in a cell culture medium with fetal bovine serum. To improve the aqueous dispersibility, the SWCNTs-(KWKG)(7) composite was further modified with polyethylene glycol ( PEG) at the lysine residues via amide bond formation and the highest modification extent of 13.3% of the amino groups which corresponded to 2 PEG chains in each peptide molecule was achieved with fluorescein isothiocyanateelabeled carboxyl-PEG12. The uptake of the SWCNTs composite by A549 human lung adenocarcinoma epithelial cells was evaluated by visual observation and fluorescence activated cell sorting analysis for SWCNTs wrapped with a mixture of ( KWKG)(7) with PEGylation and H-(-Cys-Trp-Lys-Gly-)-OH( KWKG)(6) [CWKG( KWKG)(6)] labeled with fluorescent boron-dipyrromethene tetramethylrhodamine and 7-fold higher uptake comparing with SWCNTs- peptide composite without PEGylation was obtained suggesting the importance of dispersibility in addition to a cationic charge. The superior potential of SWCNTs composites assisted by polycationic and amphiphilic peptides with PEGylation was thus demonstrated. (c) 2016 American Pharmacists Association((R)). Published by Elsevier Inc. All rights reserved.
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