Inhalation properties of water-soluble drug loaded liposomes atomized by nebulizer

Shinshu Unida,Yosuke Ito,Risako Onodera,Kohei Tahara, Hirofumi Takeuchi

Gifu Pharmaceutical University,1-25-4 Daigaku-nishi,Gifu 501-1196,Japan

Inhalation properties of water-soluble drug loaded liposomes atomized by nebulizer

Shinshu Unida*,Yosuke Ito,Risako Onodera,Kohei Tahara, Hirofumi Takeuchi

Gifu Pharmaceutical University,1-25-4 Daigaku-nishi,Gifu 501-1196,Japan

A R T I C L E I N F O

Article history:

Available online 25 November 2015

Liposome

Nebulizer

Inhalation property

Pulmonary drug delivery

The pulmonary route presents several advantages in designing drug delivery systems in both systemic and topical administration.The use of particulate carriers is an attractive method for designing pulmonary drug delivery systems, because such carriers could control drug release and selective drug targeting when the carriers reach the target site in the lung.The prevention of local irritation,reduced drug toxicity,and improved drug stability are also preferable results of utilizing such carrier systems.Among a number of particulate carriers,liposomes have an advantage in safety,because they consist of phospholipids,which are bio-components.Moreover,liposomes are able to entrap both hydrophilic and hydrophobic drugs.

In the previous study,we have reported an application of liposomes in designing a dosage form of inhales[1,2].In considering the actual dosage form design of liposomal suspension, the use of nebulizers or other inhalation systems is required. The inhalation properties of liposomal suspension are important to complete in fnal liposomal inhalation.The purpose of this study was to evaluate inhalation property and stability of liposomes after nebulization.Three nebulizer devices,namely air-jet,ultrasonic and passively vibrating mesh nebulizers were used in this study.Several types of water-soluble molecules having different molecular weights were selected as model drugs in the formulation.The water-soluble drug loaded liposomes were prepared by hydration method.Particle size of the liposomes was controlled by the extrusion method with an extruder equipped with a polycarbonate flter(100 nm).The liposomes were aerosolized by a variety of nebulizers to examine the optimal device for atomization of liposomal formulations.Furthermore,we studied the effects of physical properties of liposomes on inhalation properties.From the result of inhalation properties measured by Andersen cascade impactor(ACI),we found that the air-jet nebulizer is the most effcient device in delivering the liposomal formulations to the pulmonary parts(Fig.1).The delivery effciency to the lung decreased and the leakage of encapsulated drug increased with the increasing liposomal size.Furthermore,the small-molecular drug loaded liposomes tended to be leaked more from liposomes during atomization than macromolecular drug.However, the leakage amount of small-molecule drug depended on the particle size of liposomes and depressed by decreasing it up to 100 nm.From the above results,the air-jet nebulizer is concluded to be the most effcient devices for the nebulization ofliposomes and the particle size of liposomes is also the key factor to design the liposomal inhales.

Fig.1–ACI dispersion data of liposomes nebulized by airjet nebulizer(mean±S.D.,n=3).

R E F E R E N C E S

[1]Murata M,Nakano K,Tahara K,et al.Pulmonary delivery of elcatonin using surface-modifed liposomes to improve systemic absorption:polyvinyl alcohol with a hydrophobic anchor and chitosan oligosaccharide as effective surface modifers.Eur J Pharm Biopharm 2012;80:340–346.

[2]Murata M,Tahara K,Takeuchi H.Real-time in vivo imaging of surface-modifed liposomes to evaluate their behavior after pulmonary administration.Eur J Pharm Biopharm 2014;86:115–119.

*E-mail address:116004@gifu-pu.ac.jp.

Peer review under responsibility of Shenyang Pharmaceutical University.

http://dx.doi.org/10.1016/j.ajps.2015.11.034

1818-0876/©2016 Production and hosting by Elsevier B.V.on behalf of Shenyang Pharmaceutical University.This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).