Surface acoustic wave (SAW), a nanometer amplitude electroelastic wave generated and propagated on low-loss piezoelectric substrates (such as LiNbO3), is an extremely efficient solid–fluid energy transfer mechanism. The present study explores the use of SAW nebulization as a solution for effective pulmonary peptide delivery. In vitro deposition characteristics of the nebulized peptides were determined using a Next Generation Cascade Impactor. 70% of the peptide-laden aerosols generated were within a size distribution favorable for deep lung distribution. The integrity of the nebulized peptides was found to be retained, as shown via mass spectrometry. The anti-mycobacterial activity of the nebulized peptides was found to be uncompromised compared with their non-nebulized counterparts, as demonstrated by the minimum inhibition concentration and the colony forming inhibition activity. The peptide concentration and volume recoveries for the SAW nebulizer were significantly higher than 90% and found to be insensitive to variation in the peptide sequences. These results demonstrate the potential of the SAW nebulization platform as an effective delivery system of therapeutic peptides through the respiratory tract to the deep lung.

1.
Z. Y.
Ong
,
N.
Wiradharma
, and
Y. Y.
Yang
,
Adv. Drug Delivery Rev.
78
,
28
(
2014
).
2.
L. M.
Rossi
,
P.
Rangasamy
,
J.
Zhang
,
X. Q.
Qiu
, and
G. Y.
Wu
,
J. Pharm. Sci.
97
,
1060
(
2008
).
3.
Y.
Huang
,
N.
Wiradharma
,
K.
Xu
,
Z.
Ji
,
S.
Bi
,
L.
Li
,
Y. Y.
Yang
, and
W.
Fan
,
Biomaterials
33
,
8841
(
2012
).
4.
Y.
Lan
,
J. T.
Lam
,
G. K.
Siu
,
W. C.
Yam
,
A. J.
Mason
, and
J. K.
Lam
,
Tuberculosis
94
,
678
(
2014
).
5.
B.
Deslouches
,
J. D.
Steckbeck
,
J. K.
Craigo
,
Y.
Doi
,
J. L.
Burns
, and
R. C.
Montelaro
,
Antimicrob. Agents Chemother.
59
,
1329
(
2015
).
6.
X.
Li
,
M.
Yu
,
W.
Fan
,
Y.
Gan
,
L.
Hovgaard
, and
M.
Yang
,
Expert Opin. Drug Delivery
11
,
1435
(
2014
).
7.
M. E.
Falagas
,
I. I.
Siempos
,
P. I.
Rafailidis
,
I. P.
Korbila
,
E.
Ioannidou
, and
A.
Michalopoulos
,
Respir. Med.
103
,
707
(
2009
).
8.
M.
Sakagami
,
Ther. Delivery
4
,
1511
(
2013
).
9.
M.
Grant
and
A.
Leone-Bay
,
Ther. Delivery
3
,
981
(
2012
).
10.
M.
Irngartinger
,
V.
Camuglia
,
M.
Damm
,
J.
Goede
, and
H. W.
Frijlink
,
Eur. J. Pharm. Biopharm.
58
,
7
(
2004
).
11.
A.
Leone-Bay
,
M.
Grant
,
S.
Greene
,
G.
Stowell
,
S.
Daniels
,
A.
Smithson
,
S.
Villanueva
,
S.
Cope
,
K.
Carrera
,
S.
Reyes
, and
P.
Richardson
,
Diabetes, Obes. Metab.
11
,
1050
(
2009
).
12.
P. P.
Nadkarni
,
R. M.
Costanzo
, and
M.
Sakagami
,
Diabetes, Obes. Metab.
13
,
408
(
2011
).
13.
D.
Hubert
,
S.
Leroy
,
R.
Nove-Josserand
,
M.
Murris-Espin
,
L.
Mely
,
S.
Dominique
,
B.
Delaisi
,
P.
Kho
, and
J. M.
Kovarik
,
J. Cystic Fibrosis
8
,
332
(
2009
).
14.
American Thoracic Society and Infectious Diseases Society of America
,
Am. J. Respir. Crit. Care Med.
171
,
388
(
2005
).
15.
A.
Misra
,
A. J.
Hickey
,
C.
Rossi
,
G.
Borchard
,
H.
Terada
,
K.
Makino
,
P. B.
Fourie
, and
P.
Colombo
,
Tuberculosis
91
,
71
(
2011
).
16.
F.
Qian
,
N.
Mathias
,
P.
Moench
,
C.
Chi
,
S.
Desikan
,
M.
Hussain
, and
R. L.
Smith
,
Int. J. Pharm.
366
,
218
(
2009
).
17.
L. Y.
Yeo
,
J. R.
Friend
,
M. P.
McIntosh
,
E. N.
Meeusen
, and
D. A.
Morton
,
Expert Opin. Drug Delivery
7
,
663
(
2010
).
18.
J.
Friend
and
L. Y.
Yeo
,
Rev. Mod. Phys.
83
,
647
(
2011
).
19.
L. Y.
Yeo
and
J. R.
Friend
,
Biomicrofluidics
3
,
012002
(
2009
).
20.
X.
Ding
,
P.
Li
,
S.-C. S.
Lin
,
Z. S.
Stratton
,
N.
Nama
,
F.
Guo
,
D.
Slotcavage
,
X.
Mao
,
J.
Shi
,
F.
Costanzo
, and
T. J.
Huang
,
Lab Chip
13
,
3626
(
2013
).
21.
L. Y.
Yeo
and
J. R.
Friend
,
Annu. Rev. Fluid Mech.
46
,
379
(
2014
).
22.
G.
Destgeer
and
H. J.
Sung
,
Lab Chip
15
,
2722
(
2015
).
23.
M.
Kurosawa
,
T.
Watanabe
,
A.
Futami
, and
T.
Higuchi
,
Sens. Actuators, A
50
,
69
(
1995
).
24.
A.
Qi
,
L. Y.
Yeo
, and
J. R.
Friend
,
Phys. Fluids
20
,
074103
(
2008
).
25.
A.
Rajapaksa
,
A.
Qi
,
L. Y.
Yeo
,
R.
Coppel
, and
J. R.
Friend
,
Lab Chip
14
,
1858
(
2014
).
26.
S. R.
Heron
,
R.
Wilson
,
S. A.
Shaffer
,
D. R.
Goodlett
, and
J. M.
Cooper
,
Anal. Chem.
82
,
3985
(
2010
).
27.
J.
Ho
,
M. K.
Tan
,
D. B.
Go
,
L. Y.
Yeo
,
J. R.
Friend
, and
H.-C.
Chang
,
Anal. Chem.
83
,
3260
(
2011
).
28.
Y.
Huang
,
S. H.
Yoon
,
S. R.
Heron
,
C. D.
Masselon
,
J. S.
Edgar
,
F.
Tureček
, and
D. R.
Goodlett
,
J. Am. Soc. Mass Spectrom.
23
,
1062
(
2012
).
29.
A.
Qi
,
J. R.
Friend
,
L. Y.
Yeo
,
D. A.
Morton
,
M. P.
McIntosh
, and
L.
Spiccia
,
Lab Chip
9
,
2184
(
2009
).
30.
J. S.
Khara
,
Y.
Wang
,
X. Y.
Ke
,
S.
Liu
,
S. M.
Newton
,
P. R.
Langford
,
Y. Y.
Yang
, and
P. L.
Ee
,
Biomaterials
35
,
2032
(
2014
).
31.
Y.
Wang
,
X. Y.
Ke
,
J. S.
Khara
,
P.
Bahety
,
S.
Liu
,
S. V.
Seow
,
Y. Y.
Yang
, and
P. L.
Ee
,
Biomaterials
35
,
3102
(
2014
).
32.
A.
Qi
,
L.
Yeo
,
J.
Friend
, and
J.
Ho
,
Lab Chip
10
,
470
(
2010
).
33.
United States Pharmacopeia, Vol. 28, General Chapter ⟨601⟩ (United States Pharmacopeial Convention, Rockville, MD
,
2005
).
34.
European Pharmacopoeia 7.1 (Council of Europe, Strasbourg, France,
2011
), Section 2.9.18, pp.
274
284
.
35.
V. A.
Marple
,
B. A.
Olson
,
K.
Santhanakrishnan
,
D. L.
Roberts
,
J. P.
Mitchell
, and
B. L.
Hudson-Curtis
,
J. Aerosol Med.
17
,
335
(
2004
).
36.
D. J.
Collins
,
O.
Manor
,
A.
Winkler
,
H.
Schmidt
,
J. R.
Friend
, and
L. Y.
Yeo
,
Phys. Rev. E
86
,
056312
(
2012
).
37.
H.
Wang
,
K.
Xu
,
L.
Liu
,
J. P.
Tan
,
Y.
Chen
,
Y.
Li
,
W.
Fan
,
Z.
Wei
,
J.
Sheng
,
Y. Y.
Yang
, and
L.
Li
,
Biomaterials
31
,
2874
(
2010
).
38.
L.
Liu
,
K.
Xu
,
H.
Wang
,
P. K. J.
Tan
,
W.
Fan
,
S. S.
Venkatraman
,
L.
Li
, and
Y. Y.
Yang
,
Nat. Nanotechnol.
4
,
457
(
2009
).
39.
J.
Jaspe
and
S. J.
Hagen
,
Biophys. J.
91
,
3415
(
2006
).
40.
R. B.
Martin
,
Biopolymers
45
,
351
(
1998
).
41.
E.
Herbert
,
S.
Balibar
, and
F.
Caupin
,
Phys. Rev. E
74
,
041603
(
2006
).
42.
O.
Manor
,
L. Y.
Yeo
, and
J. R.
Friend
,
J. Fluid Mech.
707
,
482
(
2012
).
43.
J. C.
Sung
,
B. L.
Pulliam
, and
D. A.
Edwards
,
Trends. Biotechnol.
25
,
563
(
2007
).
44.
S.
Sangwan
,
J. M.
Agosti
,
L. A.
Bauer
,
B. A.
Otulana
,
R. J.
Morishige
,
D. C.
Cipolla
,
J. D.
Blanchard
, and
G. C.
Smaldone
,
J. Aerosol Med.
14
,
185
(
2001
).
45.
V.
Codrons
,
F.
Vanderbist
,
B.
Ucakar
,
V.
Preat
, and
R.
Vanbever
,
J. Pharm. Sci.
93
,
1241
(
2004
).
46.
A. E.
Rajapaksa
,
J. J.
Ho
,
A.
Qi
,
R.
Bischof
,
T. H.
Nguyen
,
M.
Tate
,
D.
Piedrafita
,
M. P.
McIntosh
,
L. Y.
Yeo
,
E.
Meeusen
,
R. L.
Coppel
, and
J. R.
Friend
,
Respir. Res.
15
,
60
(
2014
).
You do not currently have access to this content.