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

Svirkin, Yuri; Lee, Jaeweon; Marx, Richard; Yoon, Seongkyu; Landrau, Nelson; Kaisar, Md Abul; Qin, Bin; Park, Jin H.; Alam, Khondoker; Kozak, Darby; Wang, Yan; Xu, Xiaoming; Zheng, Jiwen; Rivnay, Benjamin

doi:10.1016/j.ajps.2022.04.007

Cited by 5 publications

(1 citation statement)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To date, there are not comparable data in the literature, as a similar study has not been performed yet. Svirkin et al observed a decrease in peak intensity at 415 nm after heating up to 70 °C, concluding that curing led to tighter aggregation and a decrease in drug release [ 23 ], while Liu et al compared AmBisome ® to some generical AmB formulations licensed in India and confirmed the influence of the manufacturing process on the aggregation state, drug release and toxicity [ 20 ]. However, they concluded that differences in manufacturing can induce alterations in the supramolecular structure and integrity of the liposomes, which in turn can increase the existence of free AmB, thus explaining the higher toxicity of equivalent formulations.…”

Section: Resultsmentioning

confidence: 99%

AmBisome® Formulations for Pediatrics: Stability, Cytotoxicity, and Cost-Effectiveness Studies

Zuccari,

Villa,

Iurilli

et al. 2024

Pharmaceutics

View full text Add to dashboard Cite

Liposomal amphotericin B (Ambisome®) is the gold standard for the treatment and prevention of fungal infections both in the adult and pediatric populations. The lyophilized dosage form has to be reconstituted and diluted by hospital staff, but its management can be challenging due to the spontaneous tendency of amphotericin B to form aggregates with different biological activity. In this study, the colloidal stability of the liposomes and the chemical stability of amphotericin B were investigated over time at storage conditions. Three liposomal formulations of amphotericin B at 4.0 mg/mL, 2.0 mg/mL, and 0.2 mg/mL were prepared and assayed for changes regarding the dimensional distribution, zeta potential, drug aggregation state, and onset of by-products. Our analyses highlighted that the most diluted formulation, kept at room temperature, showed the greatest changes in the aggregation state of the drug and accordingly the highest cytotoxicity. These findings are clinically relevant since the lower dosages are addressed to the more vulnerable patients. Therefore, the centralization of the dilution of AmBisome® at the pharmacy is of fundamental importance for assuring patient safety, and at the same time for reducing medication waste, as we demonstrated using the cost-saving analysis of drug expense per therapy carried out at the G. Gaslini children hospital.

show abstract

Section: Resultsmentioning

confidence: 99%