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Electrosprayed Myocet-like Liposomes: An Alternative to Traditional Liposome Production

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Abstract

Purpose

Although doxorubicin (DXR) has been on the market for many years as an anti-cancer drug, a number of serious dose-limiting toxicities hinder its widespread use. To reduce the known toxicities of soluble DXR, various liposomes have been designed including Doxil, Caelyx, and Myocet. Myocet, a non-PEGylated liposomal formulation containing DXR, was found to reduce the toxicities associated with soluble DXR and has been used in Europe and Canada (but not the US) as a first line therapy. While regarded as successful, Myocet does have some formulation drawbacks including stability, drug release, and an arduous formulation and remote loading method for preparation.

Methods

Our lab has developed a liposomal electrospray process in which formulation and remote loading occurs continuously in one step, cutting down on the total time of production and increasing the drug retention in the liposomes with respect to more conventional methods. Electrosprayed Myocet-like liposomes were then tested in vitro for release kinetics and cytotoxicity with respect to a more conventional formulation method.

Results

Myocet-like liposomes manufactured via electrospray had similar DXR loadings, hydrodynamic diameters, morphologies, and cytotoxic profiles as their thin-film hydration counterparts, but their release profiles were drastically prolonged.

Conclusions

Our findings indicate that electrospray is a viable manufacturing procedure to scalably produce Myocet-like liposomes that appear to be more stable than those formulated through thin-film hydration.

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Abbreviations

Chol:

Cholesterol

DLS:

Dynamic light scattering

DXR:

Doxorubicin

EggPC:

L-α-phosphatidylcholine from chicken egg

FDA:

Food and drug administration

HFS:

Hand-foot syndrome

TEM:

Transmission electron microscopy

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Acknowledgments and Disclosures

We would like to thank the Chapel Hill Analytical and Nanofabrication Laboratory (CHANL) for allowing us access to use the imaging equipment used within this manuscript. Also, we would like to thank the lab of Leaf Huang at UNC Chapel Hill for giving us the MCF-7 breast cancer cells. Lastly, we would like to thank Dr. Anthony D. Duong and Matthew D. Gallovic for their expertise in this area of research.

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Authors and Affiliations

  1. Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, 4211 Marsico Hall, 125 Mason Farm Road, Chapel Hill, North Carolina, 27599, USA

    Michael A. Collier, Eric M. Bachelder & Kristy M. Ainslie

Authors
  1. Michael A. Collier
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  2. Eric M. Bachelder
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  3. Kristy M. Ainslie
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Correspondence to Kristy M. Ainslie.

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Collier, M.A., Bachelder, E.M. & Ainslie, K.M. Electrosprayed Myocet-like Liposomes: An Alternative to Traditional Liposome Production. Pharm Res 34, 419–426 (2017). https://doi.org/10.1007/s11095-016-2072-4

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  • DOI: https://doi.org/10.1007/s11095-016-2072-4

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