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The Stenlying Effect of High Hydrostatic Pressure on Thermally and Hydrolytically Labile Nanosized Carriers

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Abstract

Purpose. To investigate whether high hydrostatic pressure (HHP) treatment allows the sterilization of thermosensitive polymer nanoparticle suspensions without jeopardizing their physicochemical integrity.

Methods. Application of HHP was explored on a wide variety of thermosensitive poly(cyanoacrylate) nanoparticles, varying by their type (nanospheres or nanocapsules), by their preparation method (nanoprecipitation or emulsion/solvent evaporation), as well as by their surface characteristics. Physicochemical characterization before and after pressurization included turbidimetry, size measurement, zeta potential, scanning electron microscopy and infrared analysis. A sterility test also conducted according to pharmacopoeial requirements on an importantly contaminated nanoparticle suspension.

Results. Poly(cyanoacrylate) nanoparticles appeared to be extremely baroresistant. Continuous or oscillatory HHP treatment up to 500 MPa during 30 min induced generally neither physical, nor chemical damage. However, precautions should be taken when surface modifiers are adsorbed onto nanoparticles, as a layer destabilization may occur. Finally, this process allowed the successful inactivation of vegetative bacteria, yeast, and fungi.

Conclusions. This work proposes HHP as a new method for polymer drug carriers sterilization, taking into account that further exploration in this area is needed to propose novel protocols for spores inactivation.

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Authors and Affiliations

  1. Laboratory of Biopharmacy and Pharmaceutical Technology, UMR CNRS 8612, Faculty of Pharmacy, University of Paris XI, 5, rue J.B. Clément, 92296, Châtenay-Malabry, France

    Irène Brigger, Madeleine Besnard, Antoine Andremont & Patrick Couvreur

  2. Laboratory of Bacteriology, Bichat-Claude Bernard Hospital, 75018, Paris, France

    Laurence Armand-Lefevre & Antoine Andremont

  3. Analytical Chemistry Group of Paris-South University, EA 3343, Faculty of Pharmacy, University of Paris XI, 92296, Châtenay-Malabry, France

    Pierre Chaminade

  4. Laboratory Physical-Chemistry of High Pressures (, Scientific Interface ICMCB-ENSCPB) ENSCPB, 16 Avenue Pey-Berland, 33607, Pessac cedex, France

    Yohan Rigaldie, Alain Largeteau & Gérard Demazeau

  5. Laboratory of Industrial Pharmaceutical Technology, Faculty of Pharmacy, University Victor Segalen Bordeaux II, 33076, Bordeaux, France

    Luc Grislain

Authors
  1. Irène Brigger
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  2. Laurence Armand-Lefevre
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  3. Pierre Chaminade
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  4. Madeleine Besnard
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  5. Yohan Rigaldie
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  6. Alain Largeteau
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  7. Antoine Andremont
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  8. Luc Grislain
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  9. Gérard Demazeau
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  10. Patrick Couvreur
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Correspondence to Patrick Couvreur.

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Brigger, I., Armand-Lefevre, L., Chaminade, P. et al. The Stenlying Effect of High Hydrostatic Pressure on Thermally and Hydrolytically Labile Nanosized Carriers. Pharm Res 20, 674–683 (2003). https://doi.org/10.1023/A:1023267304096

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  • DOI: https://doi.org/10.1023/A:1023267304096

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