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Comparative Investigations on In Vitro Serum Stability of Polymeric Micelle Formulations

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ABSTRACT

Purpose

Stability of polymeric micelles upon injection is essential for a drug delivery system but is not fully understood. We optimized an analytical test allowing quantification of micellar stability in biofluids and applied it to a variety of block copolymer micelles with different hydrophobic block architechtures.

Methods

Polymeric micelles were prepared from four different polymers and investigated via encapsulation of two fluorescent dyes. Samples were incubated in human serum; changes in Foerster Resonance Energy Transfer (FRET) were recorded as a function of time. This fluorescence-based approach was supported semi-quantitatively by results from Asymmetrical Flow Field-Flow-Fractionation (AF4).

Results

After incubation experiments, micellar stability was determined by calculation of two stability-indicating parameters: residual micellar fractions (RMFs) and in vitro serum half-lives. Both parameters showed that PEG-PVPy micelles rapidly destabilized after 3 h (RMF < 45%), whereas PEG-PLA, PEG-PLGA and PEG-PCL micelles were far more stable (RMFs 65 to 98%).

Conclusion

This FRET-based assay is a valuable tool in evaluating and screening serum stability of polymeric micelles and revealed low serum stability of PEG-PVPy micelles compared to polyester-based micelles.

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ACKNOWLEDGMENTS & DISCLOSURES

The authors thank Dr. Judith Kuntsche at the Martin Luther University Halle, Germany, for her help with the AF4 experiments. The support of Dr. Philip Hewitt and Alina Rwei, Merck KGaA Darmstadt, Germany, concerning language improvements is highly appreciated.

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Authors and Affiliations

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

    Tobias Miller, Ahmed Besheer, Senta Uezguen & Markus Weigandt

  2. Center for Electron Microscopy at the Institute for Anatomy, University of Regensburg, Universitätsstrasse 31, 93040, Regensburg, Germany

    Reinhard Rachel

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

    Tobias Miller & Achim Goepferich

  4. Dept. of Pharmacy, Pharmaceutical Technology & Biopharmaceutics, Ludwig Maximilians University, 81377, Munich, Germany

    Ahmed Besheer

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  1. Tobias Miller
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  2. Reinhard Rachel
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Correspondence to Achim Goepferich.

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Miller, T., Rachel, R., Besheer, A. et al. Comparative Investigations on In Vitro Serum Stability of Polymeric Micelle Formulations. Pharm Res 29, 448–459 (2012). https://doi.org/10.1007/s11095-011-0555-x

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  • DOI: https://doi.org/10.1007/s11095-011-0555-x

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