Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jan 25:669:125000.
doi: 10.1016/j.ijpharm.2024.125000. Epub 2024 Nov 27.

Reverse engineering of Onivyde® - Irinotecan liposome injection

Jingyao Gan  1 , Vivian Juang  1 , Kaikai Wang  1 , Ziyun Xia  1 , Rose Ackermann  1 , Minzhi Yu  1 , Kristen Hong Dorsey  1 , Winnie Lin  1 , Xinye Wang  1 , Yan Wang  2 , Jing Liang  2 , Jiwen Zheng  3 , Xiaoming Xu  4 , Jin H Park  2 , Anna Schwendeman  5
Affiliations

Reverse engineering of Onivyde® - Irinotecan liposome injection

Jingyao Gan et al. Int J Pharm. .

Abstract

Onivyde® is an intravenous irinotecan liposomal injection approved by the FDA for the treatment of gemcitabine-refractory metastatic adenocarcinoma of the pancreas in combination with fluorouracil and leucovorin. In the Onivyde® formulation, irinotecan is encapsulated in the inner compartment of the liposome using sucrose octasulfate as a trapping agent, and stabilized by a pegylated lipid membrane, resulting in prolonged circulation in the body. Due to its complex formulation design, there is limited information available regarding the critical quality attributes (CQAs) of Onivyde® and suitable methods for evaluating these attributes. In this study, we have developed a series of analytical methods to comprehensively characterize Onivyde®. These methods encompass particle size analysis, morphology and structure assessment, examination of physical and chemical properties, determination of drug and lipid contents, and evaluation of its release behavior in vitro.

Keywords: Analytical methods; Characterization; Drug release; Liposome; Onivyde®; Quantification.

PubMed Disclaimer

Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/ personal relationships which may be considered as potential competing interests: Anna Schwendeman reports financial support was provided by US Food and Drug Administration. Anna Schwendeman reports a relationship with EVOQ Therapeutics and ASKO Holdings that includes: board membership, consulting or advisory, equity or stocks , and funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1.
Fig. 1.
Particle size distribution of Onivyde®. The particle size distribution of Onivyde® was measured in triplicate using a Zetasizer Nano instrument. Representative curve of size distribution of Onivyde® from each batch was generated using GraphPad Prism 8.0.2 software.
Fig. 2.
Fig. 2.
Cryo-TEM images of four batches of Onivyde®. Green arrows indicate the prolate spheroid with crystal bundle inside. Yellow arrows point out round shape particles. White arrows refer to complex structures with both liposome and drug crystal inside. Red arrows indicate symmetric multilamellar vehicles. Blue arrows point out empty liposomes. A1-A2, B1-B2, C1-C2 and D1-D2 are representative cryo-TEM images of batch #120518S, batch #200048A, batch #200147A, batch #U16025 of Onivyde® respectively. Scale bar, 100 nm.
Fig. 3.
Fig. 3.
Cryo-TEM analysis of 4 batches of liposomal Onivyde® formulations. A1-A4, Feret-Max distribution of 1st to 4th batch of Onivyde® respectively. B1-B4, Feret-Min distribution of 1st to 4th batch of Onivyde® respectively. C, cryoTEM analysis. The number of observed and analyzed particles is over 500. All values are presented as mean ± SD(n ≥ 3).
Fig. 4.
Fig. 4.
Small angle X-ray scattering of Onivyde®. X-ray scattering data were collected from four batches of Onivyde®: (A), #120518S, (B), #200048A, (C), #200147A, and (D), #U16025, and the background-subtracted radially integrated scattering intensity is depicted. Data were obtained from triplicate measurements (n = 3).
Fig. 5.
Fig. 5.
The phase transition temperature of Onivyde® (#120518S (A), #200048A (B), #200147A (C), # U16025 (D)).
Fig. 6.
Fig. 6.
Representative chromatograms of DSPC (A), cholesterol (B), DSPE-PEG2k (C) standard solution, their mixture (D) and Onivyde® (E) by UPLC/ELSD.
Fig. 7.
Fig. 7.
Drug release of Onivyde® in PBS with different concentrations of ammonium bicarbonate (0 mM, 0.1 mM, 0.5 mM NH4HCO3).
Fig. 8.
Fig. 8.
Drug release of Onivyde® in 50 % human plasma. All values are presented as mean ± SD, n = 3.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Barenolz et al. Yechezkel Barenolz, Israel; Gilad Haran, Israel. 19930309. Yissum Research Development Co of Hebrew University of Jerusalem. Method of amphiphatic drug loading in liposomes by pH gradient. US5192549A.
    1. Dyer KN, Hammel M, Rambo RP, Tsutakawa SE, Rodic I, Classen S, Tainer JA, Hura GL, 2014. High-throughput SAXS for the characterization of biomolecules in solution: a practical approach. Methods Mol. Biol. 1091, 245–58. (Specific Methods paper for HT-SAXS at SIBYLS). - PMC - PubMed
    1. FDA, 2015. Onivyde®™ (irinotecan liposome injection) Label. (3836766). FDA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207793lbl.pdf.
    1. Halter M, Antia M, Vogel V, 2005. Fibronectin conformational changes induced by adsorption to liposomes. J. Control. Release 101 (1–3), 209–222. 10.1016/j.jconrel.2004.07.002. - DOI - PubMed
    1. Ipsen, 2022. Ipsen delivers strong sales growth in the first nine months of 2022 and confirms its full-year guidance. Ipsen. https://www.ipsen.com/press-releases/ipsen-delivers-strong-sales-growth-....

MeSH terms

LinkOut - more resources