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

• Type: Article in International Scientific Journal
• Date: 2020

Authors

Pashirova, TN (Author) Other; Sapunova, AS (Author) Other; Lukashenko, SS (Author) Other; Burilova, EA (Author) Other; Lubina, AP (Author) Other; Shaihutdinova, ZM (Author) Other; Gerasimova, TP (Author) Other; Kovalenko, VI (Author) Other; Voloshina, AD (Author) Other; Souto, EB (Author) Other; Zakharova, LY (Author) Other

Journal

Title: International Journal of Pharmaceutics

Vol. 575

ISSN: 0378-5173

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 9 Citations

Other information

Authenticus ID: P-00R-GDY

DOI: 10.1016/j.ijpharm.2019.118953

Abstract (EN): 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, 6, 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. 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 mu g/mL against S. aureus, B. cereus and E. coli, respectively) without hemolytic activity at 3.1 mu g/mL concentration. PC/14-Dabco-2-Dabco-14-liposomes were shown to be the best formulation, with the highest antibacterial activity against Sa (MIC = 7.8 mu g.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 PC/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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11