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Following the Concentration of Polymeric Nanoparticles During Nebulization

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Abstract

Purpose

Nebulization represents one strategy to achieve pulmonary deposition of biodegradable nanoparticles. Besides stability as a key requirement to maintain functionality, the output of nanoparticles from the nebulizer needs to be considered to facilitate an efficient pulmonary therapy.

Methods

Formulations nebulized by air-jet and vibrating-membrane technology were analyzed for their aerodynamic characteristics by laser diffraction. The nebulization stability of poly(D,L-lactide-co-glycolide) nanoparticles was assessed by dynamic light scattering. Moreover, several methods were employed to account for the shift in solute and NP reservoir concentration during nebulization.

Results

Regardless of the formulation or nebulizer used generated aerosols all showed aerodynamic characteristics suitable for deep lung deposition. However, nanoparticles were prone to aggregation and concentrated during air-jet nebulization. The particle concentration effect was significantly pronounced in comparison to molecular solutes under the same nebulization conditions, due to nanoparticle aggregation and subsequent particle remainder in the reservoir. In contrast, vibrating-membrane technology did not affect nanoparticle integrity and reservoir concentration during nebulization, as the unaffected submicron particles passed through the tapered holes of the actuated plate.

Conclusions

Aggregation and concentration effects during air-jet nebulization emphasize that nanosuspensions should preferably be delivered with a suitable vibrating-membrane device in order to ensure an effective pulmonary application.

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Abbreviations

CF:

5(6)-carboxyfluorescein

DLS:

dynamic light scattering

DMSO:

dimethyl sulfoxide

FPF:

fine particle fraction

GSD:

geometric standard deviation

LDA:

laser Doppler anemometry

MWCO:

molecular weight cut-off

NP:

nanoparticles

PDI:

polydispersity index

PLGA:

poly(D,L-lactide-co-glycolide)

S.D.:

standard deviation

TEM:

transmission electron microscopy

THF:

tetrahydrofuran

UV/Vis:

ultra violet/visible

VMD:

volume median diameter

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Acknowledgments AND DISCLOSURES

The authors would like to thank Michael Hellwig and Andreas K. Schaper (Department of Geosciences and Materials Science Center, University of Marburg) for their support with TEM. This study was supported by the German Research Foundation (DFG). We want to express our sincere thanks for this grant.

The authors disclose that no conflicting interests associated with the manuscript exist.

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Authors and Affiliations

  1. Medical Clinic II, Department of Internal Medicine, Justus-Liebig-Universität Giessen, Klinikstrasse 33, 35392, Giessen, Germany

    Moritz Beck-Broichsitter, Marie-Christine Knuedeler, Thomas Schmehl & Werner Seeger

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  1. Moritz Beck-Broichsitter
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  2. Marie-Christine Knuedeler
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  3. Thomas Schmehl
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  4. Werner Seeger
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Correspondence to Moritz Beck-Broichsitter.

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Beck-Broichsitter, M., Knuedeler, MC., Schmehl, T. et al. Following the Concentration of Polymeric Nanoparticles During Nebulization. Pharm Res 30, 16–24 (2013). https://doi.org/10.1007/s11095-012-0819-0

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  • DOI: https://doi.org/10.1007/s11095-012-0819-0

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