Medical and Pharmaceutical Aerosols - Aerosols: Measurement, Dosimetry, and Health Effects - page 12

size was shown to not signiicantly inluence the drug content in Arikace™ amikacin liposomes
after dispersion in an ACI. 127
Niosomes, which are considered to be more stable than liposomes, have been used to encapsulate
all-trans retinoic acid and have been effectively delivered by the PARI-LC STAR nebulizer with
droplet in the respiratory size and good entrapment. 128
1.3.3.3 Macromolecules
Nebulization of macromolecules has been a delicate issue, since some factors inherent to
nebulization such as shear stresses and volume have an effect on the stability and integrity of
macromolecules. 102 Furthermore, the characteristics of macromolecule solutions are often different
from those of regular solutions or suspensions, which in turn may affect nebulizer performance.
Biotechnology products frequently form viscous solutions, with modiied interfacial and surface
tension. 119 The effects of pH, additive, and ionic strength on the delivery of recombinant consensus
alpha interferon have been published. 129 It was found that interferon molecule was destabilized by
air-jet nebulizer aggregation of the plasmid. This was inluenced by pH; the smaller the pH, the
bigger the aggregation. Ionic strength of the solution did not inluence aggregation. Ultrasonic
nebulization of the solution of plasmid also resulted in aggregation but denaturation was dependent
upon the type of nebulizer used and related to the heating of nebulizer solutions.
Contradictory statements are made regarding the nebulization of proteins by ultrasonic
nebulizers. Some authors state that denaturation of proteins is unavoidable by ultrasonic nebulizers,
while others have successfully aerosolized protein solutions with this type of nebulizers. 130-132 It has
been observed that by preventing heating of the nebulizer luid during operation, denaturation of the
proteins was altered. In addition, by including 0.01% w/v Tween 80 or 1% w/v PEG 8000 almost all
activity of the proteins was retained. Therefore, cooling of the solution in conjunction with the addi-
tion of different surfactants 133 is one approach that could be used to stabilize proteins to ultrasonic
nebulization. However, cooling may also reduce solute output from the nebulizer. 134,135
Stribling et al. were among the irst to use a jet nebulizer to aerosolize plasmid/liposome vectors
to mice for the treatment of cystic ibrosis, with encouraging results. 26 Cipolla et al. 136 have also
used this approach eficiently in monkeys. A review has been published by Niven on the delivery
of biotherapeutics by inhalation aerosol. 97 It outlines the advantages of delivery of these molecules
by inhalation, stability problems when they are aerosolized, and the problems with aqueous protein
formulations, and highlights a variety of biotherapeutics given by aerosols.
1.3.4 H andHeld a queous s ysteMs
A major disadvantage of nebulizer systems has been their lack of portability. 137 The next-generation
aqueous systems include several smaller battery-powered devices that address this issue. Some
examples of these are summarized in Table 1.3. These devices typically deliver small volume doses
equivalent to those emitted from pMDIs (10-50 μL).
1.3.5 t oPical d rug d elivery s Prays
Therapeutic topical aerosols have been used for centuries for various skin diseases. Topical sprays
are used due to the ability of a spray to coat evenly the target surface with a minimum of excess
drug that may lead to undesirable effects. 138 Modern topical sprays include anti-infectives (e.g.,
tolnaftate), local anesthetics (e.g., lidocaine, benzocaine), antiseptics (phenol), scabicides (piperonyl
butoxide, pyrethrins), and sunscreens (octyl methoxycinnamate). These agents generally act locally
or topically. Subsequently, the generation of the aerosol is generally not required to have the same
stringent quality controls on particle size or dose as those aerosols used for delivery to the lungs.
However, droplet sizes are generally larger so that the probability of inertial impaction on the skin