Aerosolized amphotericin B-liposomes for treatment of systemic Candida infections in mice

Gilbert, Brian E.; Wyde, Philip R.; López-Berestein, Gabriel; Wilson, Samuel Z.

doi:10.1128/aac.38.2.356

Cited by 26 publications

(7 citation statements)

References 18 publications

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“…A logical extension of this study, then, would be to administer an AmB-lipid-based formulation in this manner. Gilbert et al (72,73) did just that in experimental models of candidiasis and cryptococcosis. The treatment significantly reduced the number of Candida organisms in the kidneys and increased the mean time of survival and percent survival of mice.…”

Section: Other Therapeutic Approachesmentioning

confidence: 99%

Carrier effects on biological activity of amphotericin B.

Brajtburg

Bolard

1996

Clinical Microbiology Reviews

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Section: Other Therapeutic Approachesmentioning

confidence: 99%

Carrier effects on biological activity of amphotericin B.

Brajtburg

Bolard

1996

Clinical Microbiology Reviews

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“…In a following up study [53] , the rate of infection was 14 and 12% for the DC-AmB and AmBisome formulations, respectively. The lipid based formulations were well tolerated Amphotericin B Liposome [124] Liposome [125] Liposome [49] Liposome [126] Liposome [48] AmB-DC [52] AmBisome [44] AmBisome [127] AmBisome [46,47] AmB-Egg PC complex [128] Abelcet [129] Abelcet [130] Itraconazole Microparticles [55,56] with nausea, vomiting and taste dysfunction reported in only 3 of 381 patients [54] . The corresponding respiratory complications were also reduced or eliminated.…”

Section: Fungal Infections and Amphotericin Bmentioning

confidence: 99%

Disease guided optimization of the respiratory delivery of microparticulate formulations

Xie

Zeng

Wiedmann

2008

Expert Opinion on Drug Delivery

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Background : Inhalation of microparticulate dosage forms can be effectively used in the treatment of respiratory and systemic diseases. Objective : Disease states investigated for treatment by inhalation of microparticles were reviewed along with the drugs' pharmacological, pharmacokinetic and physical chemical properties to identify the advantages of microparticulate inhalation formulations and to identify areas for further improvement. Methods : Microbial infections of the lung, asthma, diabetes, lung transplantation and lung cancer were examined, with a focus on those systems intended to provide a sustained release. Conclusion : In developing microparticulate formulations for inhalation in the lung, there is a need to understand the pharmacology of the drug as the key to revealing the optimal concentration time profile, the disease state, and the pharmacokinetic properties of the pure drug as determined by IV administration and inhalation. Finally, in vitro release studies will allow better identification of the best dosing strategy to be used in efficacy and safety studies.

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“…17,18 Dilauroylphosphatidylcholine (DLPC) aerosol formulations of beclomethasone and cyclosporin have already been administered in clinical settings. [31][32][33] Pharmacokinetic studies of liposome aerosols in mice with CPT showed high concentrations of CPT in the lungs, which were rapidly disseminated to the liver, tumor, brain, and other organs. 34 9-NC-DLPC liposome (LGNC) aerosols have demonstrated a favorable therapeutic index (significantly reduced tumor growth rate and shrinkage without serious side effects) in treating three different human cancer xenografts, breast, colon, and lung, in a nude mouse model.…”

Section: Aerosolized Administration Of Liposomal 9-nitrocamptothecinmentioning

confidence: 99%

“…Previous work has shown that certain drugs delivered to the respiratory tract in a liposome formulation may have advantages of noninvasive administration, including high pulmonary concentrations, often rapid entry into the systemic circulation, reduced toxicity, and reduced dosage requirements compared to oral and parenteral administration 17,18. Dilauroylphosphatidylcholine (DLPC) aerosol formulations of beclomethasone and cyclosporin have already been administered in clinical settings 31–33…”

Section: Aerosolized Administration Of Liposomal 9‐nitrocamptothecinmentioning

confidence: 99%

Alternative Administration of Camptothecin Analogues

Verschraegen

Jaeckle²,

Giovanella

et al. 2000

Annals of the New York Academy of Sciences

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The binding of camptothecin (CPT) to the DNA-topoisomerase complex is reversible, but it needs to be maintained for maximal inhibitory activity. It is also dependent on the chemical structure of CPT. The lactone form is thought to be necessary for the activity. In human serum, the equilibrium between lactone and carboxylate is in favor of the latter. For these reasons, alternative administration of CPT analogues is being evaluated. The ideal compound would remain in lactone form and would expose the host for long periods of time to its effects. Oral administration of irinotecan (CPT-11) and topotecan (TPT) is discussed by other investigators. We studied oral rubitecan and reported a low lactone to total drug area under the plasma concentrationtime curve (AUC P ) ratio (14.7%), with low plasma concentration over time despite repeated administrations and the presence of an enterohepatic cycle. Aerosolization of a liposomal formulation of rubitecan is currently under study. Six patients have been treated once a day for 5 days every 3 weeks. The dose was 6.7 g/kg/day. Plasma levels are dose for dose higher than those after oral administration, but the ratio of lactone versus total drug is low. No toxicity was observed. The study will continue with increasing doses and lengths of administration. Intrathecal administration of topotecan has been studied in a phase I trial in children. Doses of 0.4 mg are tolerated without toxicity, and clinical responses have been seen in patients with refractory meningial carcinomatosis. Phase II studies are planned. Intraperitoneal (ip) administration of topotecan has been studied in a phase I trial as a 24-hour infusion in 5% dextrose at pH 3.5 every 21 days. Dose-limiting toxicity is 4 mg/m 2 . Toxic effects are neutropenia, anemia, emesis, fever, and pain. Five of 10 patients with ascites had symptomatic relief. Pharmacokinetic analysis demonstrates a secondorder kinetics with elimination half-lives of 0.49 and 2.7 hours. The peritoneal to plasma AUC ratio was 31.2. Intramuscular, transdermal, and subcutaneous administrations have been extensively studied in the mouse.

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Aerosolized amphotericin B-liposomes for treatment of systemic Candida infections in mice

Cited by 26 publications

References 18 publications

Carrier effects on biological activity of amphotericin B.

Carrier effects on biological activity of amphotericin B.

Disease guided optimization of the respiratory delivery of microparticulate formulations

Alternative Administration of Camptothecin Analogues

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