Micellization of alkylated 1.4-diazabicyclo[2.2.2]octane by nuclear magnetic resonance technique using pulsed gradient of static magnetic field

A phenomenon of micellization of 4-aza-1-tetradecyl-1-azoniabicyclo[2.2.2] octane bromide (AB-14) in aqueous solution has been studied by the methods of nuclear magnetic resonance using magnetic field pulse gradient and fluorimetry. The critical micelle concentration is determined; concentration dependences of percentage of free AB-14 molecules and those associated with micelles as well as radii of micelles and numbers of their aggregation are established. Effect of external and internal translational diffusion of molecules on lifetime of AB-14 molecules in micelles is investigated. © 2012 Elsevier B.V

Mixed cationic liposomes for brain delivery of drugs by the intranasal route: The acetylcholinesterase reactivator 2-PAM as encapsulated drug model

© 2018 Elsevier B.V. New mixed cationic liposomes based on L-α-phosphatidylcholine and dihexadecylmethylhydroxyethylammonium bromide (DHDHAB) were designed to overcome the BBB crossing by using the intranasal route. Synthesis and self-assembly of DHDHAB were performed. A low critical association concentration (0.01 mM), good solubilization properties toward hydrophobic dye Orange OT and antimicrobial activity against gram-positive bacteria Staphylococcus aureus (MIC=7.8 μg mL–1) and Bacillus cereus (MIC=7.8 μg mL–1), low hemolytic activities against human red blood cells (less than 10%) were achieved. Conditions for preparation of cationic vesicles and mixed liposomes with excellent colloidal stability at room temperature were determined. The intranasal administration of rhodamine B-loaded cationic liposomes was shown to increase bioavailability into the brain in comparison to the intravenous injection. The cholinesterase reactivator, 2-PAM, was used as model drug for the loading in cationic liposomes. 2-PAM-loaded cationic liposomes displayed high encapsulation efficiency (∼ 90%) and hydrodynamic diameter close to 100 nm. Intranasally administered 2-PAM-loaded cationic liposomes were effective against paraoxon-induced acetylcholinesterase inhibition in the brain. 2-PAM−loaded liposomes reactivated 12 ± 1% of brain acetylcholinesterase. This promising result opens the possibility to use marketed positively charged oximes in medical countermeasures against organophosphorus poisoning for reactivation of central acetylcholinesterase by implementing a non-invasive approach, via the “nose-brain” pathway

Micellization of alkylated 1.4-diazabicyclo[2.2.2]octane by nuclear magnetic resonance technique using pulsed gradient of static magnetic field

A phenomenon of micellization of 4-aza-1-tetradecyl-1-azoniabicyclo[2.2.2] octane bromide (AB-14) in aqueous solution has been studied by the methods of nuclear magnetic resonance using magnetic field pulse gradient and fluorimetry. The critical micelle concentration is determined; concentration dependences of percentage of free AB-14 molecules and those associated with micelles as well as radii of micelles and numbers of their aggregation are established. Effect of external and internal translational diffusion of molecules on lifetime of AB-14 molecules in micelles is investigated. © 2012 Elsevier B.V

Micellization of alkylated 1.4-diazabicyclo[2.2.2]octane by nuclear magnetic resonance technique using pulsed gradient of static magnetic field

A phenomenon of micellization of 4-aza-1-tetradecyl-1-azoniabicyclo[2.2.2] octane bromide (AB-14) in aqueous solution has been studied by the methods of nuclear magnetic resonance using magnetic field pulse gradient and fluorimetry. The critical micelle concentration is determined; concentration dependences of percentage of free AB-14 molecules and those associated with micelles as well as radii of micelles and numbers of their aggregation are established. Effect of external and internal translational diffusion of molecules on lifetime of AB-14 molecules in micelles is investigated. © 2012 Elsevier B.V

Micellization of alkylated 1.4-diazabicyclo[2.2.2]octane by nuclear magnetic resonance technique using pulsed gradient of static magnetic field

A phenomenon of micellization of 4-aza-1-tetradecyl-1-azoniabicyclo[2.2.2] octane bromide (AB-14) in aqueous solution has been studied by the methods of nuclear magnetic resonance using magnetic field pulse gradient and fluorimetry. The critical micelle concentration is determined; concentration dependences of percentage of free AB-14 molecules and those associated with micelles as well as radii of micelles and numbers of their aggregation are established. Effect of external and internal translational diffusion of molecules on lifetime of AB-14 molecules in micelles is investigated. © 2012 Elsevier B.V

Mixed cationic liposomes for brain delivery of drugs by the intranasal route: The acetylcholinesterase reactivator 2-PAM as encapsulated drug model

© 2018 Elsevier B.V. New mixed cationic liposomes based on L-α-phosphatidylcholine and dihexadecylmethylhydroxyethylammonium bromide (DHDHAB) were designed to overcome the BBB crossing by using the intranasal route. Synthesis and self-assembly of DHDHAB were performed. A low critical association concentration (0.01 mM), good solubilization properties toward hydrophobic dye Orange OT and antimicrobial activity against gram-positive bacteria Staphylococcus aureus (MIC=7.8 μg mL–1) and Bacillus cereus (MIC=7.8 μg mL–1), low hemolytic activities against human red blood cells (less than 10%) were achieved. Conditions for preparation of cationic vesicles and mixed liposomes with excellent colloidal stability at room temperature were determined. The intranasal administration of rhodamine B-loaded cationic liposomes was shown to increase bioavailability into the brain in comparison to the intravenous injection. The cholinesterase reactivator, 2-PAM, was used as model drug for the loading in cationic liposomes. 2-PAM-loaded cationic liposomes displayed high encapsulation efficiency (∼ 90%) and hydrodynamic diameter close to 100 nm. Intranasally administered 2-PAM-loaded cationic liposomes were effective against paraoxon-induced acetylcholinesterase inhibition in the brain. 2-PAM−loaded liposomes reactivated 12 ± 1% of brain acetylcholinesterase. This promising result opens the possibility to use marketed positively charged oximes in medical countermeasures against organophosphorus poisoning for reactivation of central acetylcholinesterase by implementing a non-invasive approach, via the “nose-brain” pathway

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International audience(Circ. du 21 nov. 2017 relative aux règles de féminisation et de rédaction des textes

Rational Design 2-Hydroxypropylphosphonium Salts as Cancer Cell Mitochondria-Targeted Vectors: Synthesis, Structure, and Biological Properties

It has been shown for a wide range of epoxy compounds that their interaction with triphenylphosphonium triflate occurs with a high chemoselectivity and leads to the formation of (2-hydroxypropyl)triphenylphosphonium triflates 3 substituted in the 3-position with an alkoxy, alkylcarboxyl group, or halogen, which were isolated in a high yield. Using the methodology for the disclosure of epichlorohydrin with alcohols in the presence of boron trifluoride etherate, followed by the substitution of iodine for chlorine and treatment with triphenylphosphine, 2-hydroxypropyltriphenylphosphonium iodides 4 were also obtained. The molecular and supramolecular structure of the obtained phosphonium salts was established, and their high antitumor activity was revealed in relation to duodenal adenocarcinoma. The formation of liposomal systems based on phosphonium salt 3 and L-α-phosphatidylcholine (PC) was employed for improving the bioavailability and reducing the toxicity. They were produced by the thin film rehydration method and exhibited cytotoxic properties. This rational design of phosphonium salts 3 and 4 has promising potential of new vectors for targeted delivery into mitochondria of tumor cells

Synthesis, structure-activity relationship and biological evaluation of tetracationic gemini Dabco-surfactants for transdermal liposomal formulations

In this study, we report the relationship between structure, self-assembly behavior and antimicrobial activity of multicationic gemini surfactants and their successful use as stabilizers of a new liposomal formulation for transdermal drug delivery. New surfactants containing natural moiety 1,4-diazabicyclo[2.2.2]octane with four charges and two hydrophobic chains (n-Dabco-s-Dabco-n, where s=2, 12 and n=12, 14, 16, 18) were synthesized. A linear dependence of the CMC decrease, with the increase of the number of carbon atoms in alkyl groups (slope 0.23) was shown. The aggregation numbers of n-Dabco-2-Dabco-n are smaller than 30 and they decrease with increasing alkyl chain length. This is in compliance with the larger surface area per n-Dabco-2-Dabco-n molecule. New liposomal formulations loading Rhodamine B phosphatidylcholine (with mean size about 100 nm and increased zeta potential from -7±2 mV to +55±2 mV) have been successfully stabilized by n-Dabco-s-Dabco-n surfactants containing L-?- L-?-phosphatidylcholine. These formulations were designed to improve the bioavailability and skin permeation of loaded compound. The antibacterial activity of Dabco-surfactants was shown to be strongly affected by their structure (alkyl chain length and number of charged nitrogen). 12-Dabco-2-Dabco-12 was the most active (MIC=0.48, 0.98 and 15.6 µg/mL against S. aureus, B. cereus and E. coli, respectively) without hemolytic activity at 3.1 µg/mL concentration. 14-Dabco-2-Dabco-14-liposomes were shown to be the best formulation, with the highest antibacterial activity against Sa (MIC=7.8 ?g?mL1) and lowest cytotoxicity (IC50 > 125). The modification of liposomes by Dabco-surfactants stabilizes the membrane of the vesicles, preventing the release of rhodamine B and impairing the penetration of the dye across Strat-M® membrane. Cellular uptake of rhodamine B-loaded 12-Dabco-2-Dabco-12-liposomes was also reported. This is the first example of cationic mixed liposomes containing Dabco-surfactants of potential interest for transdermal drug delivery.T.N.P., S.S.L., E.A.B., A.D.V., L.Ya.Z. thank the Russian Science Foundation; grant No. 19-73-30012. E.B.S. wishes to acknowledge the Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) under the project reference MERA-NET/0004/2015 (PAIRED), co-financed by FEDER, under the Partnership Agreement PT2020. The authors gratefully acknowledge the CSF-SAC FRC KSC RAS.info:eu-repo/semantics/publishedVersio