Hoa Le, Hai V. Nguyen, Amos Abioye, Adeboye Adejare
{"title":"Formulation and Optimization of Memantine-Loaded PEGylated Single-Walled Carbon Nanotube Dispersions","authors":"Hoa Le, Hai V. Nguyen, Amos Abioye, Adeboye Adejare","doi":"10.1208/s12249-025-03194-5","DOIUrl":null,"url":null,"abstract":"<div><p>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 <i>in vitro</i> 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.</p><h3>Graphical Abstract</h3>\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 8","pages":""},"PeriodicalIF":4.0000,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"AAPS PharmSciTech","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1208/s12249-025-03194-5","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
AAPS PharmSciTech is a peer-reviewed, online-only journal committed to serving those pharmaceutical scientists and engineers interested in the research, development, and evaluation of pharmaceutical dosage forms and delivery systems, including drugs derived from biotechnology and the manufacturing science pertaining to the commercialization of such dosage forms. Because of its electronic nature, AAPS PharmSciTech aspires to utilize evolving electronic technology to enable faster and diverse mechanisms of information delivery to its readership. Submission of uninvited expert reviews and research articles are welcomed.