Optimization of single-walled carbon nanotube solubility by noncovalent PEGylation using experimental design methods
Naghmeh Hadidi1, Farzad Kobarfard2, Nastaran Nafissi-Varcheh3, Reza Aboofazeli1
1Department of Pharmaceutics, 2Department of Pharmaceutical Chemistry, 3Department of Pharmaceutical Biotechnology, School of Pharmacy, Shaheed Beheshti University of Medical Sciences, Tehran, Iran
Abstract: In this study, noncovalent functionalization of single-walled carbon nanotubes (SWCNTs) with phospholipid-polyethylene glycols (Pl-PEGs) was performed to improve the solubility of SWCNTs in aqueous solution. Two kinds of PEG derivatives, ie, Pl-PEG 2000 and Pl-PEG 5000, were used for the PEGylation process. An experimental design technique (D-optimal design and second-order polynomial equations) was applied to investigate the effect of variables on PEGylation and the solubility of SWCNTs. The type of PEG derivative was selected as a qualitative parameter, and the PEG/SWCNT weight ratio and sonication time were applied as quantitative variables for the experimental design. Optimization was performed for two responses, aqueous solubility and loading efficiency. The grafting of PEG to the carbon nanostructure was determined by thermogravimetric analysis, Raman spectroscopy, and scanning electron microscopy. Aqueous solubility and loading efficiency were determined by ultraviolet-visible spectrophotometry and measurement of free amine groups, respectively. Results showed that Pl-PEGs were grafted onto SWCNTs. Aqueous solubility of 0.84 mg/mL and loading efficiency of nearly 98% were achieved for the prepared Pl-PEG 5000-SWCNT conjugates. Evaluation of functionalized SWCNTs showed that our noncovalent functionalization protocol could considerably increase aqueous solubility, which is an essential criterion in the design of a carbon nanotube-based drug delivery system and its biodistribution.
Keywords: phospholipid-PEG, D-optimal design, loading efficiency, Raman spectroscopy, scanning electron microscopy, theromogravimetric analysis, carbon nanotubes
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