Recent advances in pulmonary drug delivery using large porous
inhaled particles.
Edwards, David A., Abdelaziz Ben-Jebria, and Robert Langer.
Department of Chemical Engineering, The Pennsylvania State
University, 204 Fenske Laboratory, University Park, PA 16802.
Department of Chemical Engineering, Massachusetts Institute of
Technology, Cambridge, MA 02139
APStracts 5:0106A, 1998.
The ability to deliver proteins and peptides to the systemic
circulation by inhalation has contributed to a rise in the number of
inhalation therapies under investigation. For most of these therapies
aerosols are designed to comprise small spherical droplets or
particles of mass density near 1 g/cm3 and mean geometric diameter
between approximately 1-3 [mu]m, suitable to particle penetration
into the airways or lung periphery. Studies performed primarily with
liquid aerosols have shown these characteristics of inhaled aerosols
lead to optimal therapeutic effect, both for local and systemic
_therapeutic delivery. Inefficient drug delivery can still arise
owing to excessive particle aggregation in an inhaler, deposition in
the mouth and throat, and overly rapid particle removal from the
lungs by mucocilliary or phagocytic clearance mechanisms. To address
these problems p_article surface chemistry and surface roughness are
traditionally manipulated. Recent data indicate that major
improvements in aerosol particle performance may_ also be achieved by
lowering particle mass density and increasing particle size, since
large porous particles display less tendency to agglomerate than
(conventional) small and nonporous particles. Also, large porous
particles inhaled into the lungs can potentially_ release therapeutic
for long periods of time by escaping phagocytic clearance from the
lung periphery, enabling therapeutic action _for periods ranging from
hours to many days.
Received 30 October 1997; accepted in final form 3 March 1998.
APS Manuscript Number A1003-7.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 6 April 1998