RESUMO
Helicobacter pylori was isolated in 1982 and confirmed as a gastric pathogenic agent at the end of the 1980s. The present work deals with liposomes formulations in which are incorporated cholesteryl tetraethylene glycol oside as model ligands for H. pylori adhesins. This study is devoted to the behavior of liposomes in gastric conditions. The glycosylated vesicles are stable and the pH of the internal aqueous compartment remains close to 4 even through more acidic conditions are imposed to the external phase (pH 1.2-2). Such a pH gradient depends essentially on the nature of phospholipids used and is not extensively affected by the incorporation of the targeting agent. These aspects are particularly important to the development of liposome formulations against H. pylori, bacteria sensitive to antibiotics which are unstable in very acidic conditions.
Assuntos
Acetilglucosamina/análogos & derivados , Antibacterianos/administração & dosagem , Colesterol/análogos & derivados , Ácido Gástrico/química , Helicobacter pylori/efeitos dos fármacos , Acetilglucosamina/química , Antibacterianos/química , Colesterol/química , Glicosilação , Concentração de Íons de Hidrogênio , LipossomosRESUMO
This paper deals with the formulation of targeted liposome against Helicobacter pylori. We describe the characterization of liposomes loaded with antimicrobial agents (ampicillin and metronidazole) and the quantification of the interactions between such formulations and bacteria. If the encapsulation rate of ampicillin seems not strongly affected by the change of phospholipidic composition, the encapsulation of metronidazole drastically decreased in epikuron 170 liposomes compared to DPPC ones. Furthermore, as observed with X-ray diffraction measurements, the presence of metronidazole results in the disorganisation of the phospholipid bilayers. Concerning the liposome-bacteria interactions, it has been observed that the incorporation of fucosyled glycolipids in the vesicle membrane leads to liposomes that are able to interact with the bacteria either in their spiral or in their coccoid forms. Since coccoid forms are occasionally found in vivo, their recognition by the liposomes we have formulated seems promising in the fight against Helicobacter pylori.
Assuntos
Glicolipídeos/química , Helicobacter pylori/efeitos dos fármacos , Lipossomos/química , Fenômenos Químicos , Química Farmacêutica , Físico-Química , Cromatografia Líquida de Alta Pressão , Composição de Medicamentos , Eletroquímica , Excipientes , Microscopia de Fluorescência , Tamanho da Partícula , Fosfolipídeos/química , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Difração de Raios XRESUMO
Lectin-sugar recognition systems are of interest in the pharmaceutical field, especially for the development of drug carriers, tailored for selective delivery. This paper deals with the anhydrous and aqueous self-organization properties of a synthetic cholesteryl oligoethyleneglycol glycoside with the aim of their incorporation in liposomes. Successive phases (lamellar, R3m, Im3m, micelles) have been described depending on water content and temperature. As a result of the presence of sugar residues and their hydration ability, this glycolipid shows a large range of packing parameter with increasing water content. However, because of oligoethyleneglycol spacer, a slight dehydration has been observed with increasing temperature from 20 to 60 degrees C.
Assuntos
Colesterol/análogos & derivados , Colesterol/química , Glicosídeos/química , Polietilenoglicóis/química , Água/química , Portadores de Fármacos/química , Estrutura MolecularRESUMO
Glycosides of cholesteryl oligoethyleneglycols have been synthesized and embedded in liposome bilayers. Several methods as steady-state fluorescence polarization, differential scanning calorimetry, zeta potential, and agglutination have been used to describe the physicochemical outcome of the incorporation of these synthetic glycolipids within phospholipid layers. From calorimetry and fluorescence experiments, it is apparent that the glycolipids decrease the transition temperature of the bilayers in a more important extent than cholesterol. Furthermore, the thickness of the aqueous layer fixed around the liposome is independent of the presence of glycolipids, suggesting that their hydrophilic parts (tetraethyleneglycol spacer and sugar moiety) are not completely extended towards the aqueous phase. Nevertheless, an important and specific interaction has been observed between such glycosylated liposomes and vegetal lectins.