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Formulation and Lyoprotection of Poly(Lactic Acid-Co-Ethylene Oxide) Nanoparticles: Influence on Physical Stability and In Vitro Cell Uptake

De Jaeghere, Fanny ; Allémann, Eric ; Leroux, Jean-Christophe ; Stevels, Wim ; Feijen, Jan ; Doelker, Eric ; Gurny, Robert

In: Pharmaceutical Research, 1999, vol. 16, no. 6, p. 859-866

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    Titre
    • Formulation and Lyoprotection of Poly(Lactic Acid-Co-Ethylene Oxide) Nanoparticles: Influence on Physical Stability and In Vitro Cell Uptake
    Auteur
    • De Jaeghere, Fanny. School of Pharmacy, University of Geneva, CH-1211, Geneva 4, Switzerland
    • Allémann, Eric. School of Pharmacy, University of Geneva, CH-1211, Geneva 4, Switzerland
    • Leroux, Jean-Christophe. Faculty of Pharmacy, University of Montreal, H3C 3J7, Montreal, Quebec, Canada
    • Stevels, Wim. Faculty of Chemical Technology, University of Twente, 7500 AE, Enschede, The Netherlands
    • Feijen, Jan. Faculty of Chemical Technology, University of Twente, 7500 AE, Enschede, The Netherlands
    • Doelker, Eric. School of Pharmacy, University of Geneva, CH-1211, Geneva 4, Switzerland
    • Gurny, Robert. School of Pharmacy, University of Geneva, CH-1211, Geneva 4, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Pharmaceutical Research, 1999, vol. 16, no. 6, p. 859-866. Kluwer Academic Publishers-Plenum Publishers
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:317419
    Summary
    Purpose. To investigate the feasibility of producing freeze-dried poly-(ethylene oxide) (PEO)-surface modified nanoparticles and to study their ability to avoid the mononuclear phagocytic system (MPS), as a function of the PEO chain length and surface density. Methods. The nanoparticles were produced by the salting-out method using blends of poly(D,L-lactic acid) (PLA) and poly(D,L-lactic acid-co-ethylene oxide) (PLA-PEO) copolymers. The nanoparticles were purified by cross-flow filtration and freeze-dried as such or with variable amounts of trehalose as a lyoprotectant. The redispersibility of the particles was determined immediately after freeze-drying and after 12 months of storage at −25° C. The uptake of the nanoparticles by human monocytes was studied in vitro by flow cytometry. Results. PLA-PEO nanoparticles could be produced from all the polymeric blends used. Particle aggregation after freeze-drying was shown to be directly related to the presence of PEO. Whereas this problem could be circumvented by use of trehalose, subsequent aggregation was shown to occur during storage. These phenomena were possibly related to the specific thermal behaviours of PEO and trehalose. In cell studies, a clear relationship between the PEO content and the decrease of uptake was demonstrated. Conclusions. The rational design of freeze-dried PEO-surface modified nanoparticles with potential MPS avoidance ability is feasible by using the polymer blends approach combined with appropriate lyoprotection and optimal storage conditions