Lipid-drug interaction: thermodynamic and structural effects of antimicotic fluconazole on DPPC liposomes

Ambrosini, Annarina; Bossi, G; Dante, Silvia; Dubini, B.; Gobbi, L.; Leone, L.; Bossi, M. G. Ponzi; Zolese, Giovanna

doi:10.1016/s0009-3084(98)00062-0

Cited by 27 publications

(14 citation statements)

References 25 publications

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“…Several reports have been published on interactions between drug compounds and lipid membrane bilayers as revealed by DSC. NSAIDS, cytostatics and antimicotics for example have been reported to interfere with phase transitions (Ambrosini et al, 1998;Beni et al, 2006;Kyrikou et al, 2004).…”

Section: Influence Of Drug Substances On the Phospholipid Vesicle Basmentioning

confidence: 99%

Drug permeability across a phospholipid vesicle based barrier: 3. Characterization of drug–membrane interactions and the effect of agitation on the barrier integrity and on the permeability

Flaten¹,

Skar²,

Luthman³

et al. 2007

European Journal of Pharmaceutical Sciences

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Recently we reported on the development and structural characterization of a phospholipid vesicle based barrier useful for medium throughput screening of passive drug permeability.Here, we investigate the physical and functional integrity of the phospholipid vesicle based barriers to agitation by stirring or shaking, and whether agitation affects drug permeability of sulpiride, metoprolol and testosterone. In addition, three drugs (caffeine, naproxen and sulphasalazine) which were shown in a previous study to affect the electrical resistance of the barriers, were investigated for their influence on the permeability of a simultaneously applied hydrophilic marker (calcein), and on the thermotropic phase transition of the phospholipid bilayers using differential scanning calorimetry (DSC).Electrical resistance measurements indicated that the barriers should withstand shaking speeds up to 150 rpm without losing their integrity, but significant release of phospholipids from the membrane barriers to the donor and acceptor chambers was observed under agitation ≥150 rpm. When using agitation up to 100 rpm no increase in permeability was observed for sulpiride, metoprolol and testosterone. The phospholipid vesicle-based barrier thus differ from other permeability models in that agitation does not lead to an increase in permeability, not even for highly lipophilic drugs such as testosterone. This is explained by the different morphology of the vesicle-based barrier which is containing a 100 µm thick layer of mostly aqueous compartments immobilised within a matrix of phospholipids vesicles.Sulphasalazine and naproxen were shown to decrease the electrical resistance and increase the permeability of the hydrophilic marker calcein. The DSC experiments showed that these two drugs probably interact with the head groups of the phospholipids. In contrast, caffeine gave an increase in electrical resistance and a decrease in permeability of calcein. From the DSC experiments no signs of interaction of caffeine with the phospholipid bilayer could be observed.3

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Section: Influence Of Drug Substances On the Phospholipid Vesicle Basmentioning

confidence: 99%

Drug permeability across a phospholipid vesicle based barrier: 3. Characterization of drug–membrane interactions and the effect of agitation on the barrier integrity and on the permeability

Flaten¹,

Skar²,

Luthman³

et al. 2007

European Journal of Pharmaceutical Sciences

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“…The high penetration into the aqueous humor and low toxicity of fluconazole make it a good candidate for consideration as a topical ocular antifungal agent (Abbasoglu et al, 2001). The azole antifungal drugs inhibit the biosynthesis of ergosterol, the major sterol found in the fungal cell membrane, which is essential for the regulation of membrane fluidity and integrity and for fungal growth and proliferation (Ambrosini et al, 1998). Although topical fluconazole solutions in experimental Candida keratitis have proved to be effective, with good penetration into the cornea and aqueous humor, liposomal penetrations were still thought to provide potentially longer contact time, allowing greater penetration of the fluconazole (BehrensBaumann et al, 1990;Yee et al, 1997;Yilmaz and Maden, 2005).…”

Section: Introductionmentioning

confidence: 99%

Effect of formulation design and freeze-drying on properties of fluconazole multilamellar liposomes

El-Nesr

Yahiya

El‐Gazayerly

2010

Saudi Pharmaceutical Journal

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Fluconazole-entrapped multilamellar liposomes were prepared using the thin-film hydration method. The effects of cholesterol molar ratio, charge-inducing agents, and α-tocopherol acetate on encapsulation efficiency values and in vitro drug release of multilamellar liposomes were studied. Freeze-dried liposomal products were prepared with or without cryoprotectants. Results showed that incorporation of stearylamine resulted in an increased entrapment of fluconazole, whereas incorporation of dicetyl phosphate decreased the drug entrapment efficiency. The incorporation of α-tocopherol acetate into fluconazole multilamellar liposomes resulted in the increase of entrapment efficiency of fluconazole liposomes. In vitro release studies revealed that incorporation of cholesterol into multilamellar liposomal formulations decreased drug permeability from formulations. Positively charged fluconazole multilamellar liposomes gave rise to a slow release rate compared to neutral liposomes whereas negatively charged fluconazole liposomes showed a rapid release rate. Physical stability studies showed that lyophilized cake of liposomes without cryoprotectants was compact and difficult to reconstitute compared to fluffy easily reconstituted cakes upon using cryoprotectants. Fluconazole retained in freeze-dried liposomes without cryoprotectants was 63.452% compared to 91.877% using three grams of trehalose as a cryoprotectant per gram lipid in positively charged multilamellar liposomes. Physical stability studies showed superior potentials of the lyophilized product after reconstitution in comparison with those of a solution product.

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“…The high penetration into the aqueous humour and low toxicity of fluconazole, make it a good candidate for consideration as a topical ocular antifungal agent (Abbasoglu et al 2001). The azole antifungal drugs inhibit biosynthesis of ergosterol, the major sterol found in the fungal cell membrane, which is essential to the regulation of membrane fluidity and integrity and to fungal growth and proliferation (Ambrosini et al 1998).…”

Section: Introductionmentioning

confidence: 99%

Liposomes as an ocular delivery system of fluconazole: in‐vitro studies

Habib

Fouad

Abdel-Rhaman

et al. 2010

Acta Ophthalmologica

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Acta Ophthalmol. 2010: 88: 901–904 Abstract. Purpose: To study the clinical effect of topical controlled‐release ophthalmic fluconazole liposomal formulation and to compare its effect with fluconazole solution in a reproducible model of Candida keratitis in rabbits. Methods: Forty adult rabbits were included in this study. Right eyes were inoculated with freshly prepared Caindida albicans strain no. 4925 and showed signs of infected keratitis. The rabbits were divided randomly into two groups: in the first group (18 rabbits) the right eyes received fluconazole solution, while in the second group (22 rabbits) the right eyes received fluconazole‐loaded liposomes. The rabbits’ eyes were examined daily over a 21‐day period and results were recorded. Results: Rabbits infected with C. albicans responded better and showed more improvement in terms of size of ulcer and hypopyon using fluconazole‐loaded liposomal formulae than using fluconazole solution. In the first group (solution), nine rabbits’ cornea showed complete healing (50%) at the end of third week while in group 2 (liposome), 19 rabbits’ cornea showed complete healing (86.4%) at equal duration. These results were statistically significant. Conclusion: Therapy with topical liposomal fluconazole (2 mg/ml) was successful in eliminating experimental C. albicans infection of the rabbit cornea and was superior to fluconazole solution.

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Lipid-drug interaction: thermodynamic and structural effects of antimicotic fluconazole on DPPC liposomes

Cited by 27 publications

References 25 publications

Drug permeability across a phospholipid vesicle based barrier: 3. Characterization of drug–membrane interactions and the effect of agitation on the barrier integrity and on the permeability

Drug permeability across a phospholipid vesicle based barrier: 3. Characterization of drug–membrane interactions and the effect of agitation on the barrier integrity and on the permeability

Effect of formulation design and freeze-drying on properties of fluconazole multilamellar liposomes

Liposomes as an ocular delivery system of fluconazole: in‐vitro studies

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