Molecular insights into the aggregation and solubilizing behavior of biocompatible amphiphiles Gelucire® 48/16 and Tetronics® 1304 in aqueous media

A comparative analysis of the micellar and solubilizing properties of two polyethylene glycol (PEG)-based amphiphilic biocompatible excipients: Gelucire® 48/16 (Ge 48/16) and Tetronics® 1304 (T1304), in the presence and absence of salt, was conducted. As there is a dearth of research in this area, the study aims to shed light on the behavior of these two nonionic surfactants and their potential as nanocarriers for solubilizing pharmaceuticals. Various techniques such as cloud point (CP), dynamic light scattering (DLS), small-angle neutron scattering (SANS), Fourier transform infrared spectroscopy (FT-IR), UV spectrophotometry, and high-performance liquid chromatography (HPLC) were employed. The solubility of quercetin (QCT), a flavonoid with anti-inflammatory, antioxidant, and anti-cancer properties, was evaluated and the interaction between QCT and the micellar system was examined. The analysis revealed the occurrence of strong interactions between QCT and surfactant molecules, resulting in enhanced solubility. It was observed that the micellar size and solubilizing ability were significantly improved in the presence of salt, while the CP decreased. Ge 48/16 exhibited superior performance, with a remarkable increase in the solubility of QCT in the presence of salt, suggesting its potential as an effective nanocarrier for a range of pharmaceutics, and yielding better therapeutic outcomes.

2.1 Materials

The nonionic surfactants Gelucire® 48/16 (Ge 48/16) and Tetronics® 1304 (T1304) with the chemical structure illustrated in Fig. 1 were provided as free samples by Gattefossé, India, and BASF Corp., India, respectively. The samples were used as received without any further purification. The salt, sodium chloride (NaCl) with purity ∼99% and analytical grade was purchased from Sigma Aldrich (India). The samples for measurements were prepared using deionized water from Milipore Mili-Q system except for SANS where 99.9 atom% pure D₂O, purchased from sigma Aldrich (India), was used for the sample preparation.

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Deep Bhalani, Hiral Kakkadz, Jignasa Modh, Debes Ray, Vinod K. Aswal and Sadafara A. Pillai, Molecular insights into the aggregation and solubilizing behavior of biocompatible amphiphiles Gelucire® 48/16 and Tetronics® 1304 in aqueous media, RSC Adv., 2023, 13, 28590-28601
https://doi.org/10.1039/D3RA04844F