Analytical method development and comparability study for AmBisome® and generic Amphotericin B liposomal products

Liu, Yayuan; Mei, Zihan; Mei, Ling; Tang, Jie; Yuan, Wenjie; Srinivasan, Santhanakrishnan; Ackermann, Rose; Schwendeman, Anna

doi:10.1016/j.ejpb.2020.09.008

Cited by 17 publications

(11 citation statements)

References 42 publications

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“…When analyzed by NTA, the same formulations always had a mean diameter slightly smaller than that determined by DLS ( Table 2 , Figure S1 ). This result is in contrast with the findings of Liu et al [ 20 ], whose study revealed always larger values for NTA-based measurements. This slight discrepancy among the two research studies may lie in the difficulty in characterizing nano-systems like liposomes linked to the complexity of manufacturing processes and reproducibility of the scale-up, all factors that may influence the uniformity of the batches.…”

Section: Resultscontrasting

confidence: 99%

“…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%

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

Zuccari,

Villa,

Iurilli

et al. 2024

Pharmaceutics

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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.

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Section: Resultscontrasting

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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

Zuccari,

Villa,

Iurilli

et al. 2024

Pharmaceutics

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“…Under the physiological pH, different head groups provide liposomes with negative (PA, PS, PG, and cardiolipin) or neutral (PC and PE) charges [49]. Negatively charged DSPG used in AmBisome (ambisome liposome for injection) can interact with the positively charged amine group of AmpB to form a stable ionic complex [50], while DSPG used in Vyxeos minimize liposome aggregation by a strong Coulombic repulsive force [51]. DSPC used in DaunoXome (daunorubicin citrate liposome injection), Onivyde (irinotecan liposome injection), and Vyxeos is a neutral and synthetic lipid with well-defined fatty acid composition (two molecules of stearic acid), high purity, and a relatively high phase transition (T m of 55 • C).…”

Section: Main Components Of Liposomesmentioning

confidence: 99%

A Review of Liposomes as a Drug Delivery System: Current Status of Approved Products, Regulatory Environments, and Future Perspectives

Liu¹,

Chen²,

Zhang³

2022

Molecules

566

239

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Liposomes have been considered promising and versatile drug vesicles. Compared with traditional drug delivery systems, liposomes exhibit better properties, including site-targeting, sustained or controlled release, protection of drugs from degradation and clearance, superior therapeutic effects, and lower toxic side effects. Given these merits, several liposomal drug products have been successfully approved and used in clinics over the last couple of decades. In this review, the liposomal drug products approved by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) are discussed. Based on the published approval package in the FDA and European public assessment report (EPAR) in EMA, the critical chemistry information and mature pharmaceutical technologies applied in the marketed liposomal products, including the lipid excipient, manufacturing methods, nanosizing technique, drug loading methods, as well as critical quality attributions (CQAs) of products, are introduced. Additionally, the current regulatory guidance and future perspectives related to liposomal products are summarized. This knowledge can be used for research and development of the liposomal drug candidates under various pipelines, including the laboratory bench, pilot plant, and commercial manufacturing.

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“…The recent development of a method for measuring AmB release from liposomes under sink conditions [ 75 ] led to the demonstration that “heat curing” of liposomal AmB resulted in a reduced rate of AmB release [ 76 ]. Thus, the authors proposed that the release rate of AmB is the link between the AmB aggregation state in the liposomal bilayer and the in vitro toxicity of the formulation.…”

Section: Reduced Toxicity Of Liposomal Amb Formulations: Role Of the ...mentioning

confidence: 99%

“… Kinetics of release of AmB at 55 °C from conventional and PEGylated liposomal AmB (LAmB and PEG-LAmB, respectively) prepared according to [ 77 ], and AmBisome ® . Dialysis was performed using Spectra-Por ® Float-A-Lyzer ® G2 MWCO 100kDa in the presence of 5% γ-cyclodextrin, according to [ 76 ]. …”

Section: Figurementioning

confidence: 99%

Liposomal Amphotericin B for Treatment of Leishmaniasis: From the Identification of Critical Physicochemical Attributes to the Design of Effective Topical and Oral Formulations

et al. 2022

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The liposomal amphotericin B (AmB) formulation, AmBisome®, still represents the best therapeutic option for cutaneous and visceral leishmaniasis. However, its clinical efficacy depends on the patient’s immunological status, the clinical manifestation and the endemic region. Moreover, the need for parenteral administration, its side effects and high cost significantly limit its use in developing countries. This review reports the progress achieved thus far toward the understanding of the mechanism responsible for the reduced toxicity of liposomal AmB formulations and the factors that influence their efficacy against leishmaniasis. It also presents the recent advances in the development of more effective liposomal AmB formulations, including topical and oral liposome formulations. The critical role of the AmB aggregation state and release rate in the reduction of drug toxicity and in the drug efficacy by non-invasive routes is emphasized. This paper is expected to guide future research and development of innovative liposomal formulations of AmB.

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Analytical method development and comparability study for AmBisome® and generic Amphotericin B liposomal products

Cited by 17 publications

References 42 publications

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

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

A Review of Liposomes as a Drug Delivery System: Current Status of Approved Products, Regulatory Environments, and Future Perspectives

Liposomal Amphotericin B for Treatment of Leishmaniasis: From the Identification of Critical Physicochemical Attributes to the Design of Effective Topical and Oral Formulations

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