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Drug Loading of Polymeric Micelles

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ABSTRACT

Purpose

To gain mechanistic insights into drug loading and lyophilization of polymeric micelles.

Methods

PEGylated poly-4-(vinylpyridine) micelles were loaded with dexamethasone. Three different methods were applied and compared: O/W emulsion, direct dialysis, cosolvent evaporation. Micellar dispersions with the highest drug load were lyophilized with varying lyoprotectors: sucrose, trehalose, maltose, a polyvinylpyrrolidine derivative, and β-cyclodextrin derivatives. For comparison, other PEGylated block copolymer micelles (PEGylated polylactic acid, polylactic acid-co-glycolic acid, polycaprolactone) were freeze-dried.

Results

Drug loading via direct dialysis from acetone was a less effective loading method which led to dexamethasone loads <2% w/w. O/W emulsion technique from dichlormethane increased drug load up to ~13% w/w; optimized cosolvent evaporation increased load up to ~19% w/w. An important step for cosolvent evaporation was solubility screen of the drug prior to preparation. Loading was maintained upon lyophilization with β-cyclodextrins which proved to be versatile stabilizers for other block copolymer micelles.

Conclusion

Careful solvent selection prior to cosolvent evaporation was a beneficial approach to load hydrophobic drugs into polymeric micelles. Moreover, β-cyclodextrins could be used as versatile lyoprotectors for these micelles.

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ACKNOWLEDGMENTS AND DISCLOSURES

We are grateful to Golshah Ayoubi for expert technical assistance. The Centre for Stochastic Geometry and Advanced Bioimaging is supported by the Villum Foundation.

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Author notes

  1. Tobias Miller

    Present address: Georgia Institute of Technology, Dept. for Biomedical Engineering, 313 Ferst Drive, Atlanta, Georgia, 30332, USA

Authors and Affiliations

  1. Merck KGaA, Exploratory Pharmaceutical Development, Frankfurter Straße 250, 64293, Darmstadt, Germany

    Tobias Miller, Gwenaelle van Colen, Senta Uezguen & Markus Weigandt

  2. Stereology and EM Laboratory, Dept. of Clinical Medicine, University of Aarhus, Wilhelm Meyers Allé 3, 8000, Aarhus C, Denmark

    Bjoern Sander

  3. Centre for Stochastic Geometry and Advanced Bioimaging, University of Aarhus, 8000, Aarhus C, Denmark

    Bjoern Sander & Mariola Monika Golas

  4. Dept. of Biomedicine, University of Aarhus, Wilhelm Meyers Allé 3, 8000, Aarhus C, Denmark

    Mariola Monika Golas

  5. Department of Pharmaceutical Technology, University of Regensburg, Universitätsstrasse 31, 93040, Regensburg, Germany

    Tobias Miller & Achim Goepferich

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Correspondence to Achim Goepferich.

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Miller, T., van Colen, G., Sander, B. et al. Drug Loading of Polymeric Micelles. Pharm Res 30, 584–595 (2013). https://doi.org/10.1007/s11095-012-0903-5

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  • DOI: https://doi.org/10.1007/s11095-012-0903-5

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