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Aerosol Delivery of Nanoparticles in Uniform Mannitol Carriers Formulated by Ultrasonic Spray Freeze Drying

Pharmaceutical Research volume 30, pages 2891–2901 (2013)Cite this article

Abstract

Purpose

While most examples of nanoparticle therapeutics have involved parenteral or IV administration, pulmonary delivery is an attractive alternative, especially to target and treat local infections and diseases of the lungs. We describe a successful dry powder formulation which is capable of delivering nanoparticles to the lungs with good aerosolization properties, high loadings of nanoparticles, and limited irreversible aggregation.

Methods

Aerosolizable mannitol carrier particles that encapsulate nanoparticles with dense PEG coatings were prepared by a combination of ultrasonic atomization and spray freeze drying. This process was contrasted to particle formation by conventional spray drying.

Results

Spray freeze drying a solution of nanoparticles and mannitol (2 wt% solids) resulted in particles with an average diameter of 21 ± 1.7 μm, regardless of the fraction of nanoparticles loaded (0–50% of total solids). Spray freeze dried (SFD) powders with a 50% nanoparticle loading had a fine particle fraction (FPF) of 60%. After formulation in a mannitol matrix, nanoparticles redispersed in water to < 1 μm with hand agitation and to < 250 nm with the aid of sonication. Powder production by spray drying was less successful, with low powder yields and extensive, irreversible aggregation of nanoparticles evident upon rehydration.

Conclusions

This study reveals the unique advantages of processing by ultrasonic spray freeze drying to produce aerosol dry powders with controlled properties for the delivery of therapeutic nanoparticles to the lungs.

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Abbreviations

da :

Aerodynamic diameter

DPI:

Dry powder inhaler

EtTP-5:

2,2,10,10-tetraethyl-6,14-bis (triisopropylsilylethynyl)- 1,3,9,11-tetraoxadicyclopenta [b,m] pentacene fluorescent dye

FPF:

Fine particle fraction

LN2:

Liquid nitrogen

NGI:

Next generation impactor

NP:

Nanoparticle

NPAC:

NP aerosol carriers

PLA3.8k-b-PEG5k-OCH3 :

Polylactide-b-poly(ethylene glycol)

PSD:

Particle size distribution

PVA:

Polyvinyl alcohol

SD:

Spray dry

SFD:

Spray freeze dry

THF:

Tetrahydrofuran

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Acknowledgments And Disclosures

This work made use of the Confocal & Electron Microscopy Core Facility at Princeton University and the authors acknowledge Joe Goodhouse for expert help with confocal microscopy. This work was supported through National Science Foundation and the Australian Academy of Science as part of the East Asia and South Pacific Summer Institutes Fellowship (1015344) and through grants from the Australian Research Council (DP0985367 & 120102778).

Author information

Author notes

  1. Philip Chi Lip Kwok

    Present address: Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR

Affiliations

  1. Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney, Pharmacy Building A15, Camperdown, New South Wales, 2006, Australia

    Suzanne M. D’Addio, John Gar Yan Chan, Philip Chi Lip Kwok & Hak-Kim Chan

  2. Chemical and Biological Engineering, Princeton University, Princeton, New Jersey, 08854, USA

    Suzanne M. D’Addio, Bryan R. Benson & Robert K. Prud’homme

Authors
  1. Suzanne M. D’Addio
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  2. John Gar Yan Chan
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  3. Philip Chi Lip Kwok
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  4. Bryan R. Benson
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  5. Robert K. Prud’homme
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  6. Hak-Kim Chan
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Corresponding authors

Correspondence to Robert K. Prud’homme or Hak-Kim Chan.

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D’Addio, S.M., Chan, J.G.Y., Kwok, P.C.L. et al. Aerosol Delivery of Nanoparticles in Uniform Mannitol Carriers Formulated by Ultrasonic Spray Freeze Drying. Pharm Res 30, 2891–2901 (2013). https://doi.org/10.1007/s11095-013-1120-6

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  • DOI: https://doi.org/10.1007/s11095-013-1120-6

KEY WORDS

  • drug delivery
  • nanoparticle aerosol carriers
  • NPAC
  • spray drying
  • spray freeze drying