Characterization and aerosol dispersion performance of advanced spray-dried chemotherapeutic PEGylated phospholipid particles for dry powder inhalation delivery in lung cancer

Samantha A. Meenach, Kimberly W. Anderson, J. Zach Hilt, Ronald C. McGarry, Heidi - Mansour

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Pulmonary inhalation chemotherapeutic drug delivery offers many advantages for lung cancer patients in comparison to conventional systemic chemotherapy. Inhalable particles are advantageous in their ability to deliver drug deep in the lung by utilizing optimally sized particles and higher local drug dose delivery. In this work, spray-dried and co-spray dried inhalable lung surfactant-mimic PEGylated lipopolymers as microparticulate/nanoparticulate dry powders containing paclitaxel were rationally designed via organic solution advanced spray drying (no water) in closed-mode from dilute concentration feed solution. Dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine poly(ethylene glycol) (DPPE-PEG) with varying PEG chain length were mixed with varying amounts of paclitaxel in methanol to produce co-spray dried microparticles and nanoparticles. Scanning electron microscopy showed the spherical particle morphology of the inhalable particles. Thermal analysis and X-ray powder diffraction confirmed the retention of the phospholipid bilayer structure in the solid-state following spray drying, the degree of solid-state molecular order, and solid-state phase transition behavior. The residual water content of the particles was very low as quantified analytically Karl Fisher titration. The amount of paclitaxel loaded into the particles was quantified which indicated high encapsulation efficiencies (43-99%). Dry powder aerosol dispersion performance was measured in vitro using the Next Generation Impactor™ (NGI™) coupled with the Handihaler® dry powder inhaler device and showed mass median aerodynamic diameters in the range of 3.4-7 lm. These results demonstrate that this novel microparticulate/nanoparticulate chemotherapeutic PEGylated phospholipid dry powder inhalation aerosol platform has great potential in lung cancer drug delivery.

Original languageEnglish (US)
Pages (from-to)699-711
Number of pages13
JournalEuropean Journal of Pharmaceutical Sciences
Volume49
Issue number4
DOIs
StatePublished - 2013

Fingerprint

Paclitaxel
Aerosols
Powders
Inhalation
Lung Neoplasms
Phospholipids
Lung
Inhalation Administration
Pharmaceutical Preparations
Dry Powder Inhalers
Powder Diffraction
1,2-Dipalmitoylphosphatidylcholine
Ethylene Glycol
Water
Phase Transition
Surface-Active Agents
X-Ray Diffraction
Electron Scanning Microscopy
Nanoparticles
Methanol

Keywords

  • Biocompatible biodegradable lipopolymers
  • Dry powder inhaler (DPI)
  • Lung surfactant
  • Nanomedicine
  • Nanotechnology
  • Respiratory drug delivery

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Characterization and aerosol dispersion performance of advanced spray-dried chemotherapeutic PEGylated phospholipid particles for dry powder inhalation delivery in lung cancer. / Meenach, Samantha A.; Anderson, Kimberly W.; Zach Hilt, J.; McGarry, Ronald C.; Mansour, Heidi -.

In: European Journal of Pharmaceutical Sciences, Vol. 49, No. 4, 2013, p. 699-711.

Research output: Contribution to journalArticle

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