Nebulization and Upper Airway Deposition of Liposomal Carrier Systems

Overview

Journal Mol Pharm

Publisher American Chemical Society

Specialty Pharmacology

Date 2024 Mar 11

PMID 38466817

Authors

Ondrej Misik

Jana Kejikova

Ondrej Cejpek

Milan Maly

Adam Jugl

Miloslav Belka

Filip Mravec

Frantisek Lizal

Affiliations

Soon will be listed here.

Abstract

Liposomal carrier systems have emerged as a promising technology for pulmonary drug delivery. This study focuses on two selected liposomal systems, namely, dipalmitoylphosphatidylcholine stabilized by phosphatidic acid and cholesterol (DPPC-PA-Chol) and dipalmitoylphosphatidylcholine stabilized by polyethylene glycol and cholesterol (DPPC-PEG-Chol). First, the research investigates the stability of these liposomal systems during the atomization process using different kinds of nebulizers (air-jet, vibrating mesh, and ultrasonic). The study further explores the aerodynamic particle size distribution of the aerosol generated by the nebulizers. The nebulizer that demonstrated optimal stability and particle size was selected for more detailed investigation, including Andersen cascade impactor measurements, an assessment of the influence of flow rate and breathing profiles on aerosol particle size, and an deposition study on a realistic replica of the upper airways. The most suitable combination of a nebulizer and liposomal system was DPPC-PA-Chol nebulized by a Pari LC Sprint Star in terms of stability and particle size. The influence of the inspiration flow rate on the particle size was not very strong but was not negligible either (decrease of by 1.34 μm with the flow rate increase from 8 to 60 L/min). A similar effect was observed for realistic transient inhalation. According to the deposition measurement, approximately 90% and 70% of the aerosol penetrated downstream of the trachea using the stationary flow rate and the realistic breathing profile, respectively. These data provide an image of the potential applicability of liposomal carrier systems for nebulizer therapy. Regional lung drug deposition is patient-specific; therefore, deposition results might vary for different airway geometries. However, deposition measurement with realistic boundary conditions (airway geometry, breathing profile) brings a more realistic image of the drug delivery by the selected technology. Our results show how much data from cascade impactor testing or estimates from the fine fraction concept differ from those of a more realistic case.

Citing Articles

Inhalational Drug Devices: Revisiting the Linchpin of Asthma Management.

Saxena D, Murugesan N, Evbayiro U, Ngassa M, Adrish M J Pers Med. 2024; 14(8).

PMID: 39202058 PMC: 11355058. DOI: 10.3390/jpm14080867.

References

Moradpour Z, Barghi L . Novel Approaches for Efficient Delivery of Tyrosine Kinase Inhibitors. J Pharm Pharm Sci. 2019; 22(1):37-48. DOI: 10.18433/jpps29891. View

Lippmann M, Albert R . The effect of particle size on the regional deposition of inhaled aerosols in the human respiratory tract. Am Ind Hyg Assoc J. 1969; 30(3):257-75. DOI: 10.1080/00028896909343120. View

Sercombe L, Veerati T, Moheimani F, Wu S, Sood A, Hua S . Advances and Challenges of Liposome Assisted Drug Delivery. Front Pharmacol. 2015; 6:286. PMC: 4664963. DOI: 10.3389/fphar.2015.00286. View

Golshahi L, Noga M, Vehring R, Finlay W . An in vitro study on the deposition of micrometer-sized particles in the extrathoracic airways of adults during tidal oral breathing. Ann Biomed Eng. 2013; 41(5):979-89. DOI: 10.1007/s10439-013-0747-0. View

Elhissi A . Liposomes for Pulmonary Drug Delivery: The Role of Formulation and Inhalation Device Design. Curr Pharm Des. 2016; 23(3):362-372. DOI: 10.2174/1381612823666161116114732. View

Lehofer B, Bloder F, Jain P, Marsh L, Leitinger G, Olschewski H . Impact of atomization technique on the stability and transport efficiency of nebulized liposomes harboring different surface characteristics. Eur J Pharm Biopharm. 2014; 88(3):1076-85. DOI: 10.1016/j.ejpb.2014.10.009. View

Chow A, Tong H, Chattopadhyay P, Shekunov B . Particle engineering for pulmonary drug delivery. Pharm Res. 2007; 24(3):411-37. DOI: 10.1007/s11095-006-9174-3. View

Elhissi A, Gill H, Ahmed W, Taylor K . Vibrating-mesh nebulization of liposomes generated using an ethanol-based proliposome technology. J Liposome Res. 2010; 21(2):173-80. DOI: 10.3109/08982104.2010.505574. View

Rudokas M, Najlah M, Albed Alhnan M, Elhissi A . Liposome Delivery Systems for Inhalation: A Critical Review Highlighting Formulation Issues and Anticancer Applications. Med Princ Pract. 2016; 25 Suppl 2:60-72. PMC: 5588529. DOI: 10.1159/000445116. View

10.

Hu J, Zhang R, Beng H, Deng L, Ke Q, Tan W . Effects of flow pattern, device and formulation on particle size distribution of nebulized aerosol. Int J Pharm. 2019; 560:35-46. DOI: 10.1016/j.ijpharm.2019.01.025. View

11.

Kaul H . Respiratory healthcare by design: Computational approaches bringing respiratory precision and personalised medicine closer to bedside. Morphologie. 2019; 103(343):194-202. DOI: 10.1016/j.morpho.2019.10.042. View

12.

Liu Q, Guan J, Qin L, Zhang X, Mao S . Physicochemical properties affecting the fate of nanoparticles in pulmonary drug delivery. Drug Discov Today. 2019; 25(1):150-159. DOI: 10.1016/j.drudis.2019.09.023. View

13.

Pilcer G, Amighi K . Formulation strategy and use of excipients in pulmonary drug delivery. Int J Pharm. 2010; 392(1-2):1-19. DOI: 10.1016/j.ijpharm.2010.03.017. View

14.

Wang Y, Li J, Leavey A, ONeil C, Babcock H, Biswas P . Comparative Study on the Size Distributions, Respiratory Deposition, and Transport of Particles Generated from Commonly Used Medical Nebulizers. J Aerosol Med Pulm Drug Deliv. 2016; 30(2):132-140. DOI: 10.1089/jamp.2016.1340. View

15.

Darquenne C, Prisk G . Deposition of inhaled particles in the human lung is more peripheral in lunar than in normal gravity. Eur J Appl Physiol. 2008; 103(6):687-95. DOI: 10.1007/s00421-008-0766-y. View

16.

Mitchell J, Copley M, Sizer Y, Russell T, Solomon D . Adapting the Abbreviated Impactor Measurement (AIM) concept to make appropriate inhaler aerosol measurements to compare with clinical data: a scoping study with the "Alberta" idealized throat (AIT) inlet. J Aerosol Med Pulm Drug Deliv. 2012; 25(4):188-97. DOI: 10.1089/jamp.2011.0925. View

17.

Niven R, Schreier H . Nebulization of liposomes. I. Effects of lipid composition. Pharm Res. 1990; 7(11):1127-33. DOI: 10.1023/a:1015924124180. View

18.

Carvalho T, Peters J, Williams 3rd R . Influence of particle size on regional lung deposition--what evidence is there?. Int J Pharm. 2011; 406(1-2):1-10. DOI: 10.1016/j.ijpharm.2010.12.040. View

19.

Lizal F, Belka M, Adam J, Jedelsky J, Jicha M . A method for in vitro regional aerosol deposition measurement in a model of the human tracheobronchial tree by the positron emission tomography. Proc Inst Mech Eng H. 2015; 229(10):750-7. DOI: 10.1177/0954411915600005. View

20.

Berkenfeld K, Hauschild K, McConville J, Lamprecht A . Cascade Impactor Performance of Commercial pMDI Formulations Using Modified Induction Ports. Mol Pharm. 2020; 17(5):1491-1501. DOI: 10.1021/acs.molpharmaceut.9b01171. View