Dry powder aerosol delivery of large hollow nanoparticulate aggregates as prospective carriers of nanoparticulate drugs: Effects of phospholipids

Dry powder aerosol delivery of large hollow nanoparticulate aggregates as prospective carriers of nanoparticulate drugs: Effects of phospholipids
Received 5 June 2006; revised 29 August 2006; accepted 6 October 2006. Available online 10 October 2006
Kunn Hadinotoa, , , Ponpan Phanapavudhikula, Zhu Kewua and Reginald B.H. Tana, b
International Journal of Pharmaceutics
Volume 333, Issues 1-2, 21 March 2007
ScienceDirect
Copyright ? 2006 Elsevier B.V. All rights reserved
aA*STAR Institute of Chemical and Engineering Sciences, Singapore 627833, Singapore
bDepartment of Chemical & Biomolecular Engineering, National University of Singapore, Singapore 119260, Singapore
Abstract
The present work details the effects of incorporating phospholipids, a major component of lung surfactants, in the formulation of large hollow nanoparticulate aggregates, which are specifically designed to serve as potential carrier particles in inhaled delivery of nanoparticulate drugs. The large hollow aerosol particles (dg ? 10 ?m), whose shells are composed of nanoparticulate aggregates, are manufactured via the spray drying of nanoparticulate suspensions under a predetermined operating condition. Polyacrylate and silica nanoparticles of various sizes (20?170 nm), without loaded drugs, are employed as the model nanoparticles. The effects of increasing the phospholipids concentration in the presence of the nanoparticles, and vice versa, on the degree of hollowness and morphology of the spray-dried particles are investigated. Varying the phospholipids concentration in the presence of a constant amount of nanoparticles is found to influence the degree of hollowness, without significantly affecting the particle size distribution and respirable fine particle fraction, of the aerosol particles. The effects of increasing the phospholipids concentration on the degree of hollowness of the spray-dried particles are found to depend on the size and chemical nature of the nanoparticles.
Keywords: Dry powder inhaler; Inhaled drug delivery; Pulmonary delivery; Nanoparticulate drugs; Spray drying; Hollow particles
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