Synthesis, Properties, and Biomedical Application of Dicationic Gemini Surfactants with Dodecane Spacer and Carbamate Fragments

Abstract

A synthesis procedure and aggregation properties of a new homologous series of dicationic gemini surfactants with a dodecane spacer and two carbamate fragments (N,N′-dialkyl-N,N′-bis(2-(ethylcarbamoyloxy)ethyl)-N,N′-dimethyldodecan-1,6-diammonium dibromide, n-12-n(Et), where n = 10, 12, 14) were comprehensively described. The critical micelle concentrations of gemini surfactants were obtained using tensiometry, conductometry, spectrophotometry, and fluorimetry. The thermodynamic parameters of adsorption and micellization, i.e., maximum surface excess (Гmax), the surface area per surfactant molecule (Amin), degree of counterion binding (β), and Gibbs free energy of micellization (∆Gmic), were calculated. Functional activity of the surfactants, including the solubilizing capacity toward Orange OT and indomethacin, incorporation into the lipid bilayer, minimum inhibitory concentration, and minimum bactericidal and fungicidal concentrations, was determined. Synthesized gemini surfactants were further used for the modification of liposomes dual-loaded with α-tocopherol and donepezil hydrochloride for intranasal treatment of Alzheimer’s disease. The obtained liposomes have high stability (more than 5 months), a significant positive charge (approximately + 40 mV), and a high degree of encapsulation efficiency toward rhodamine B, α-tocopherol, and donepezil hydrochloride. Korsmeyer-Peppas, Higuchi, and first-order kinetic models were used to process the in vitro release curves of donepezil hydrochloride. Intranasal administration of liposomes loaded with α-tocopherol and donepezil hydrochloride for 21 days prevented memory impairment and decreased the number of Aβ plaques by 37.6%, 40.5%, and 72.6% in the entorhinal cortex, DG, and CA1 areas of the hippocampus of the brain of transgenic mice with Alzheimer’s disease model (APP/PS1) compared with untreated animals.

Mitochondria-Targeted Lipid Nanoparticles Loaded with Rotenone as a New Approach for the Treatment of Oncological Diseases

“…For a more detailed understanding of the kinetics of the ROT release from the liposomes, the obtained dependencies were processed by two kinetic models, namely, the Korsmeyer-Peppas and Higuchi models (Figure 10 and Figure S5, respectively). Based on personal experience and the literature data, these two models have proven most suitable for characterizing the kinetics of substrate release from liposomes [36,73,[75][76][77][78]. According to the presented graphs (Figure 10), the Korsmeyer-Peppas model better described the release profiles of ROT from the modified liposomes than the Higuchi model (Figure S5), because the correlation coefficient (R 2 ) in all the cases exceeded 0.98 (Table 3).…”

“…The absorption spectra of ROT for all the systems are shown in Figures S6-S11. can also be explained in terms of a decrease in the critical micelle concentration with an increase in the surfactant hydrocarbon tail length [70,71], which can lead to an increase in the ability of the surfactants to loosen the lipid bilayer and leakage of ROT from liposomes [72][73][74]. However, it should be noted that the differences between the surfactants with C16 and C10 did not exceed 10%.…”