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https://hdl.handle.net/1822/63821
Título: | Synthesis, structure-activity relationship and biological evaluation of tetracationic gemini Dabco-surfactants for transdermal liposomal formulations |
Autor(es): | Pashirova, T. N. Sapunova, A. S. Lukashenko, S. S. Burilova, E. A. Lubina, A. P. Shaihutdinova, Z. M. Gerasimova, T. P. Kovalenko, V. I. Voloshina, A. D. Souto, Eliana B. Zakharova, L. Ya. |
Palavras-chave: | Quaternary ammonium derivatives of 1, 4-diazabicyclo[2.2.2]octane liposomes cationic surfactants solubilization antimicrobial activity skin permeation |
Data: | 15-Fev-2020 |
Editora: | Elsevier 1 |
Revista: | International Journal of Pharmaceutics |
Citação: | Pashirova, T. N.; Sapunova, A. S.; Lukashenko, S. S.; Burilova, E. A.; Lubina, A. P.; Shaihutdinova, Z. M.; Gerasimova, T. P.; Kovalenko, V. I.; Voloshina, A. D.; Souto, Eliana; Zakharova, L. Ya., Synthesis, structure-activity relationship and biological evaluation of tetracationic gemini Dabco-surfactants for transdermal liposomal formulations. International Journal of Pharmaceutics, 575(118953), 2020 |
Resumo(s): | 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. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/63821 |
DOI: | 10.1016/j.ijpharm.2019.118953 |
ISSN: | 0378-5173 |
Versão da editora: | http://www.elsevier.com/locate/issn/03785173 |
Arbitragem científica: | yes |
Acesso: | Acesso restrito UMinho |
Aparece nas coleções: | CEB - Publicações em Revistas/Séries Internacionais / Publications in International Journals/Series |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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document_52292_1.pdf Acesso restrito! | 1,87 MB | Adobe PDF | Ver/Abrir |