A kinetic method for measuring functional delivery of amphotericin B by drug delivery systems

Amphotericin B release rate is the link between drug status in the liposomal bilayer and toxicity

“…Toxicity of lipid formulations was also shown to depend on particle size and lamellarity [40] , [41] , [42] , [43] , on the nature of and relative concentration of the sterol(s), and the drug-to-lipid ratios [44] , [45] , [46] . Studies on these parameters involved in vivo studies (mice or rats), in vitro cell lines [47 , 48] and surrogate toxicity testing systems like potassium release in erythrocytes [28 , 49] , or artificial system models for toxicity [15 , 50] . While the effects of the lipids on toxicity may be partially derived from influencing the equilibria amongst different aggregate forms in the liposomes, this could also be related to liposome-cell (membrane), liposome-lipoprotein, and liposome-albumin interactions in vivo (affecting pharmacodynamics and pharmacokinetics).…”

“…The authors in both studies suggested the reduced toxicity was related to the rate of drug transfer to the target membrane but stopped short of measuring drug release rates [46 , 56] . Peterson et al [50] also showed that variations of lipid compositions influenced toxicity (potassium release) in target membranes without discussing curing or aggregation. They, too, stated that the drug release rates could be responsible for the variations but did not directly measure drug release rates [50] .…”

“…Peterson et al [50] also showed that variations of lipid compositions influenced toxicity (potassium release) in target membranes without discussing curing or aggregation. They, too, stated that the drug release rates could be responsible for the variations but did not directly measure drug release rates [50] .…”

Amphotericin B-induced ion flux is markedly attenuated in phosphatidylglycerol membrane as evidenced by a newly devised fluorometric method

“…[20][21][22][23][24] The membrane-permeabilizing antibiotics have been studied using artificial liposomes with various methods. 19,[23][24][25][26][27][28][29] Among them, a fluorometric method using dye-encapsulated liposomes is effective for the real-time monitoring of ion flux, which enable the detection of minute difference in the activity. 10,12,29 In this report we aimed to establish a real-time monitoring method for measuring the membrane-permeabilizing activity of AmB and examined the influence of head groups of phospholipids on the drug's activity.…”