In-vivo studies of amphotericin B liposomes derived from proliposomes: effect of formulation on toxicity and tissue disposition of the drug in mice

Payne, Nicholas I.; Cosgrove, R. F.; Green, A. P.; Liu, Lin

doi:10.1111/j.2042-7158.1987.tb07156.x

Cited by 40 publications

(11 citation statements)

References 19 publications

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“…Thus, the organ distribution in mice obtained with AmB incorporated in SUV EPC/TS 7:3 was found to be similar to that obtained with fungizone [153]. In contrast, with other formulations, liposomal AmB was found to accumulate in the lung [118] or in the liver [45,97]. Data for serum indicated slightly lower levels of AmB when added as the liposomal preparation [45].…”

Section: In Vivomentioning

confidence: 77%

“…One of the difficulties encountered in the comparison of the various studies performed in vivo and in vitro is the multiplicity of the liposomal systems used. The following liposomes have mainly been used: MLY constituted of sphingomyelin and ergosterol [45], of 0 MPC/DMPG (7 :3) with or without sterol [95], of various PC with DMPG [118]; polymerized vesicles [107]; SUY constituted of EPCI cholesterol/tocopherol succinate (5:3: 1) and prepared in a bath -sonicator [157]; or SUY prepared with a probe sonicator [73]. In general, AmB was added during the liposome preparation except in two types of experiments where it was added after [72,73,107], which has the advantage of avoiding the degradation due to sonication.…”

Section: Constitution and Nature Of Liposomal Ambmentioning

confidence: 99%

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Mechanism of Action of an Anti-Candida Drug: Amphotericin B and Its Derivatives

Bolard

1991

Candida Albicans

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Section: In Vivomentioning

confidence: 77%

Section: Constitution and Nature Of Liposomal Ambmentioning

confidence: 99%

Mechanism of Action of an Anti-Candida Drug: Amphotericin B and Its Derivatives

Bolard

1991

Candida Albicans

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“…The early clinical results of treatment with liposomal preparations of AmB are very interesting and should be expanded. The development of proliposomes (28) can help to overcome the difficulties connected with the standardization and stabilization of liposome preparations. Recent efforts at targeting AmB to antigenic sites on fungi by using liposomal AmB formulations with attached specific antibodies might further increase the therapeutic efficacy of AmB (12,13).…”

Section: Discussionmentioning

confidence: 99%

Amphotericin B: delivery systems

Brajtburg

Powderly

Kobayashi

et al. 1990

Antimicrob Agents Chemother

110

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INTRODUCTIONAmphotericin B (AmB) is insoluble in aqueous solution and before it can be used clinically as an antifungal agent to treat systemic mycosis, a vehicle (carrier) has to be added to form a dispersion. The commercial preparation of AmB, Fungizone, is a mixture of AmB, a detergent deoxycholate, and a buffer. When suspended in a glucose solution, Fungizone forms a colloidal dispersion suitable for intravenous injection. AmB can also-be obtained as a dispersion by addition of a concentrated AmB solution in organic solvents to water; this preparation has been used in several in vitro studies on the cellular and molecular effects of AmB. Because the clinical utility of AmB is limited by its toxicity to host cells, an important question is how to best direct it specifically to the fungus or at least to the site of infection or, alternatively, how to keep it away from the host cells. One strategy is to use a vehicle other than deoxycholate. In this minireview, we review some of the relevant studies addressing this issue. LIPOSOMESThe term liposome is used here interchangeably with the term lipid vesicles and refers to phospholipid bilayers of one or more closed concentric structures. The first attempt to use antifungal agents in combination with liposomes was guided by the previous findings of an enhancement of the antileishmanial activity of antimony compounds by liposomes (27). The rationale for the work on AmB was that because both the parasites and liposomes were taken up by phagocytic cells, the AmB entrapped in the liposomes might be brought into close proximity to the parasite inside the host macrophages. Results of this work demonstrated that preparations of liposomal AmB were less toxic to the host and had higher therapeutic capability than dispersions of free AmB.In subsequent studies, liposomes have been used as vehicles for AmB in treatment of murine histoplasmosis (31), cryptococcosis (8), and candidiasis (24). In all of these experimental systems, as well as in additional studies (for references, see references 20 and 32), liposomal AmB was shown to be as potent as the free drug against infecting fungi, whereas its toxicity to the host was decreased. The lower level of toxicity permitted larger doses to be given, and consequently the liposomal formulations were more effective than free AmB against fungal infections in the animal models used. three pilot clinical studies on the use of liposomal AmB in cancer patients with fungal infections (21,22,29). Patients tolerated liposomal AmB much better than AmB in the form of Fungizone. Increased doses could be administered, and a significant clinical improvement was observed in some patients. Although these studies are difficult to evaluate because the patients had advanced neoplastic disease and multiple concurrent therapies, the results justify further investigation. As Sculier et al. (29) emphasized, the type of liposomal vehicle (chemical composition, charge, structure, and mode of preparation) can modify the physicochemical, biological, and pharmac...

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“…Thus some physicochemical and biological properties are also enhanced in the complex. The proven successes in promoting the absorption of a variety of natural substances by phospholipids complex formation include silybin (15), dilichol (16), saponins from Centella asiatica (17), herba epimedii total flavonoids (18), baicalin (19), diclofenac (20) and piroxicam (21).…”

Section: Introductionmentioning

confidence: 99%