The aerosol properties of niosomes were studied using Aeroneb Pro and Omron MicroAir vibrating-mesh nebulizers and Pari LC Sprint air-jet nebulizer. Proniosomes were prepared by coating sucrose particles with Span 60 (sorbitan monostearate), cholesterol and beclometasone dipropionate (BDP) (1:1:0.1). Nano-sized niosomes were produced by manual shaking of the proniosomes in deionized water followed by sonication (median size 236 nm). The entrapment of BDP in proniosome-derived niosomes was higher than that in conventional thin film-made niosomes, being 36.4% and 27.5% respectively. All nebulizers generated aerosols with very high drug output, which was 83.6% using the Aeroneb Pro, 85.5% using the Pari and 72.4% using the Omron. The median droplet size was 3.32 m, 3.06 m and 4.86 m for the Aeroneb Pro, Pari and Omron nebulizers respectively and the “fine particle fraction” (FPF) of BDP was respectively 68.7%, 76.2% and 42.1%. The predicted extrathoracic deposition, based on size distribution of nebulized droplets was negligible for all devices, suggesting all of them are potentially suitable for pulmonary delivery of niosomes. The predicted drug deposition in the alveolar region was low using the Omron (3.2%), but greater using the Aeroneb Pro (17.4%) and the Pari (20.5%). Overall, noisome- BDP aerosols with high drug output and FPF can be generated from proniosomes and delivered using vibrating-mesh or air-jet nebulizers.
Bibliographical noteReference text: Albasarah, Y.Y., Somavarapu, S., Stapleton, P., Taylor, K.M., 2010. Chitosan-coated
antifungal formulations for nebulisation. J. Pharm. Pharmacol. 62, 821–828.
Abd-Elbary, A., El-Laithy, H.M., Tadros, M.I., 2008. Sucrose stearate-based
pronisomes-derived niosomes for the nebulisable delivery of cromolyn sodium.
Int. J. Pharm. 357, 189–198.
Batavia, R., Taylor, K.M.G., Craig, D.Q.M., Thomas, M., 2001. The measurement of
beclomethasone dipropionate entrapment in liposomes: a comparison of a
microscope and an HPLC method. Int. J. Pharm. 212, 109–119.
Bridges, P.A., Taylor, K.M.G., 2000. The effects of freeze-drying on the stability of
liposomes to jet nebulization. J. Pharm. Pharmacol. 53, 393–398.
Clark, A.R., 1995. The use of laser diffraction for the evaluation of the aerosol clouds
generated by medical nebulizers. Int. J. Pharm. 115, 69–78.
Clay, M.M., Pavia, D., Newman, S.P., Lennard-Jones, T., Clarke, S.W., 1983. Assessment
of jet nebulisers for lung aerosol therapy. Lancet 2, 592–594.
Crommelin, D.J., 1984. Influence of lipid composition and ionic strength on the
physical stability of liposomes. J. Pharm. Sci. 73, 1559–1563.
Crowe, L.M., Crowe, J.H., 1988. Trehalose and dry dipalmitoylphosphatidylcholine
revisted. Biochim. Biophys. Acta 946, 193–201.
Dahlbنck, M., 1994. Behavior of nebulizing solutions and suspensions. J. Aerosol
Med. 7 (Suppl. 1), S13–S18.
Darwis, Y., Kellaway, I.W., 2001. Nebulisation of rehydrated freeze-dried
beclomethasone dipropionate liposomes. Int. J. Pharm. 215, 113–121.
Desai, T.R., Finlay, W.H., 2002. Nebulization of niosomal all-trans-retinoic acid: an
inexpensive alternative to conventional liposomes. Int. J. Pharm. 241, 311–317.
Dhand, R., 2002. Nebulizers that use a vibrating mesh or plate with multiple apertures
to generate aerosol. Respir. Care 47, 1406–1416.
Elhissi, A.M.A., Taylor, K.M.G., 2005. Delivery of liposomes generated from proliposomes
using air-jet, ultrasonic and vibrating-mesh nebulisers. J. Drug Del. Sci.
Technol. 15, 261–265.
Elhissi, A.M.A., Karnam, K.K., Danesh, M.R., Gill, H.S., Taylor, K.M.G., 2006a. Formulations
generated from ethanol-based proliposomes for delivery via medical
nebulizers. J. Pharm. Pharmacol. 58, 887–894.
Elhissi, A.M.A., O’Neill, M.A.A., Roberts, S.A., Taylor, K.M.G., 2006b. A calorimetric
study of dimyristoylphosphatidylcholine phase transitions and
steroid–liposome interactions for liposomes prepared by thin film and
proliposome methods. Int. J. Pharm. 320, 124–130.
Elhissi, A.M., Faizi, M., Naji, W.F., Gill, H.S., Taylor, K.M., 2007. Physical stability and
aerosol properties of liposomes delivered using an air-jet nebulizer and a novel
micropump device with large mesh apertures. Int. J. Pharm. 334, 62–70.
Elhissi, A., Gill, H., Ahmed, W., Taylor, K., 2011a. Vibrating-mesh nebulization of liposomes
generated using an ethanol-based proliposome technology. J. Liposome
Res. 21, 173–180.
Elhissi, A.M.A., O’Neill, M., Ahmed, W., Taylor, K.M.G., 2011b. High sensitivity differential
scanning calorimetry for measurement of steroid entrapment in nebulised
liposomes generated from proliposomes. Micro Nano Lett. 6, 694–697.
Ghazanfari, T., Elhissi, A.M., Ding, Z., Taylor, K.M., 2007. The influence of fluid
physicochemical properties on vibrating-mesh nebulization. Int. J. Pharm. 339,
Hao, Y-M., Li, K., 2011. Entrapment and release difference resulting from hydrogen
bonding interactions in niosomes. Int. J. Pharm. 403, 245–253.
Heyder, J., 1982. Particle transport onto human airway surfaces. Eur. J. Respir. Dis.
Suppl. 119, 29–50.
Hu, C., Rhodes, D.G., 1999. Proniosomes: a novel drug carrier preparation. Int. J.
Pharm. 206, 110–122.
Junyaprasert, V.B., Teeranachaideekul, V., Supaperm, T., 2008. Effect of charged and
non-ionic membrane additives on physicochemical properties and stability of
niosomes. AAPS Pharm. SciTech. 9, 851–859.
Kellaway, I.W., Farr, S.J., 1990. Liposomes as drug delivery systems to the lung. Adv.
Drug Deliv. Rev. 5, 149–161.
Kwong, W.T.J., Ho, S.L., Coates, A.L., 2000. Comparison of nebulized particle size
distribution with Malvern laser diffraction analyzer versus Andersen Cascade
Impactor and Low-flow Marple Personal Cascade Impactor. J. Aerosol Med. 13,
Lange, C.F., Hancock, R.E.W., Samuel, J., Finlay, W.H., 2001. In vitro aerosol delivery
and regional airway surface liquid concentration of a liposomal cationic peptide.
J. Pharm. Sci. 90, 1647–1657.
Mosharraf, M., Taylor, K.M., Craig, D.Q., 1995. Effect of calcium ions on the surface
charge and aggregation of phosphatidylcholine liposomes. J. Drug Target.
Nasr, M., Nawaz, S., Elhissi, A.M.A., 2012. Amphotericin B lipid nanoemulsion
aerosols for targeting peripheral respiratory airways via nebulization. Int. J.
Pharm. 436, 611–616.
Newman, S., Gee-Turner, A., 2005. The Omron MicroAir vibrating mesh technology
nebuliser, a 21st century approach to inhalation therapy. Drug Deliv. Syst. Sci.
Niven, R.W., Speer, M., Schreier, H., 1991. Nebulization of liposomes. II. The
effects of size and modeling of solute release profiles. Pharm. Res. 8,
None, L.V., Grimbert, D., Becquemin, M.H., Boissinot, E., Le Pape, A., Lemarié, E.,
Diot, P., 2001. Validation of laser diffraction method as a substitute for cascade
impaction in the European Project for a nebulizer standard. J. Aerosol. Med. 14,
O’Callaghan, C., Barry, P.W., 1997. The science of nebulised drug delivery. Thorax 52
(Suppl. 2), S31–S44.
Ofir, E., Oren, Y., Adin, A., 2007. Electroflocculation: the effect of zeta-potential on
particle size. Desalination 204, 33–38.
Payne, N.I., Timmins, P., Ambrose, C.V., Ward, M.D., Ridgway, F., 1986. Proliposomes:
a novel solution to an old problem. J. Pharm. Sci. 75, 325–329.
Puglia, C., Rizza, L., Drechsler, M., Bonina, F., 2010. Nanoemulsions as vehicles for
topical administration of glycyrrhetic acid: characterization and in vitro and
in vivo evaluation. Drug Deliv. 17, 123–129.
Saari, M., Vidgren, M.T., Koskinen, M.O., Turjanmaa, V.M.H., Nieminen, M.M., 1999.
Pulmonary distribution and clearance of two beclomethasone formulations in
healthy volunteers. Int. J. Pharm. 181, 1–9.
Taylor, K.M.G., Taylor, G., Kellaway, I.W., Stevens, J., 1989. The influence of liposomal
encapsulation on sodium cromoglicate pharmacokinetics in man. Pharm. Res. 6,
Taylor, K.M.G., Taylor, G., Kellaway, I.W., Stevens, J., 1990. The stability of liposomes
to nebulisation. Int. J. Pharm. 58, 57–61.
Terzano, C., Allegra, L., Alhaique, F., Marianecci, C., Carafa, M., 2005. Nonphospholipid
vesicles for pulmonary glucocorticoid delivery. Eur. J. Pharm.
Biopharm. 59, 57–62.
Uchegbu, I.F., Florence, A.T., 1995. Non-ionic surfactant vesicles (niosomes): physical
and pharmaceutical chemistry. Adv. Colloid Interface Sci. 58, 1–55.
Uchegbu, I.F., Vyas, S.P., 1998. Non ionic surfactant based vesicles (niosomes) in drug
delivery. Int. J. Pharm. 172, 33–70.
Van Bommel, E.M.G., Crommelin, D.J.A., 1984. Stability of doxorubicin–liposomes
on storage: as an aqueous dispersion, frozen or freeze-dried. Int. J. Pharm. 22,
Van Winden, E.C.A., Talsma, H., Crommelin, D.J.A., 1998. Thermal analysis of
freeze-dried liposome–carbohydrate mixtures with modulated temperature
differential scanning calorimetry. J. Pharm. Sci. 87, 231–237.
Van Winden, E.C.A., Crommelin, D.J.A., 1997. Long term stability of freeze-dried,
lyoprotected doxorubicin liposomes. Eur. J. Pharm. Biopharm. 43, 295–307.
Waldrep, J.C., Scherer, P.W., Hess, G.D., Black, M., Knight, V., 1994. Nebulized glucocorticoids
in liposomes: aerosol characteristics and human dose estimates. J.
Aerosol Med. 7, 135–145.
Zaru, M., Mourtas, S., Klepetsanis, P., Fadda, A.M., Antimisiaris, S.G., 2007. Liposomes
for drug delivery to the lungs by nebulization. Eur. J. Pharm. Biopharm. 67,
- Beclometasone dipropionate