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 a L a 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 ug/mL against S. aureus, B. cereus and E. coli, respectively) without hemolytic activity at 3.1 ug/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 mg.mL 1) 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(r) 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.
International journal of pharmaceutics