Formulation and Optimization of Memantine-Loaded PEGylated Single-Walled Carbon Nanotube Dispersions

The study aimed to develop stable single-walled carbon nanotube (SWCNT) dispersions in water that exhibit low protein adsorption in biological media, entrap Memantine, and release the drug in a controlled manner. Specifically, SWCNTs were functionalized, initially oxidized, and then non-covalently conjugated with pyrene methoxy polyethylene glycols (PEG). Dynamic light scattering, Raman spectroscopy, and Fourier-transform infrared spectroscopy were used to evaluate various physicochemical properties of PEG functionalized SWCNTs (PEGSWCNTs). A D-optimal design, utilizing JMP Pro 16, was employed to design the experiment and investigate the effects of oxidation time and PEG concentration on the physicochemical properties of SWCNT dispersions. The optimal dispersions exhibited hydrodynamic particle sizes, polydispersity indices, and zeta potentials ranging from 157.5 to 204.4 nm, 0.231 to 0.255, and -27.8 to -18.8 mV, respectively. The interaction between serum proteins and PEGSWCNTs was evaluated using dynamic light scattering, bicinchoninic acid, and sodium dodecyl sulfate–polyacrylamide gel electrophoresis. The serum protein–SWCNT interaction was significantly reduced due to the presence of PEGs, depending on PEG concentrations, the ratio of long-chain PEG molecules to short-chain PEG molecules, and the physicochemical properties of PEGSWCNT dispersions. Finally, Memantine was incorporated into the optimal PEGSWCNT dispersions. The entrapment efficiency, drug loading, and drug release from the dispersions were evaluated using gas chromatography with flame ionization detection (GC/FID). The results indicated that PEGSWCNT particles could entrap Memantine. The in vitro drug release profile exhibited an extended release over 3 to 7 h, with a significant burst release occurring in the first hour (more than 50%). Higher PEG density and a higher PEG20K/2K ratio exhibited slower drug release rates. The release profiles of the formulations using 40% PEG were fitted to the Weibull model, indicating that Memantine release from the SWCNT dispersions followed a Fickian diffusion mechanism.

Graphical Abstract