In vitro pulmonary cell culture in pharmaceutical inhalation aerosol delivery: 2-D, 3-D, and in situ bioimpactor models

Maria F. Acosta, Priya Muralidharan, Samantha A. Meenach, Don Hayes, Stephen M. Black, Heidi M. Mansour

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: The use of non-invasive inhaled aerosols for pulmonary drug delivery continues to grow. This is due to the many unique advantages this delivery route offers for the treatment of both local and systemic diseases. The physicochemical properties of the formulated drugs as well as the physiology of the lungs play a key role in both the deposition and absorption of the particles. The airway and the alveolar epithelium are targets for the treatment of respiratory diseases. However, particles have to overcome biological barriers before they reach their target and produce an effect. Methods: In vitro aerosol dispersion performance (i.e. aerodynamic size and aerodynamic size distribution) of inhalable particles is quantified by inertial impaction, as required by regulatory agencies for an investigational pharmaceutical inhalation aerosol formulation to be approved for use in patients as a marketed pharmaceutical product. Using inertial impaction in conjunction with cell cultures of various pulmonary cells in situ as bioimpactors has unique aspects in correlating aerodynamic properties with pulmonary cellular behavior including viability and uptake. These can be as co-culture or in single culture, as 3-D multicellular spheroids or 2-D cellular monolayer using different conditions to grow them, such as air-liquid interface culture (ALI) or in liquid covered culture (LCC). Results: evaluation of the currently available in vitro models and the challenges in developing reliable cellular tools to predict the deposition of inhalable particles in the lungs as a function of aerodynamic particle properties is presented in the manuscript. Conclusion: The mechanistic aerodynamic and biophysical properties of inhaled aerosol particles on the entire respiratory tract at the cellular level based on aerodynamic size and aerodynamic size distribution will be better understood with the development of in vitro methods which are described in this work.

Original languageEnglish (US)
Pages (from-to)2522-2531
Number of pages10
JournalCurrent Pharmaceutical Design
Volume22
Issue number17
StatePublished - May 1 2016

Fingerprint

Aerosols
Inhalation
Cell Culture Techniques
Lung
Pharmaceutical Preparations
Cellular Spheroids
Investigational Drugs
Manuscripts
Coculture Techniques
Respiratory System
Epithelium
Air
In Vitro Techniques
Therapeutics

Keywords

  • Aerosol deposition
  • Air-liquid interface (ALI) culture
  • Liquid covered culture (LCC)
  • Lung cell culture
  • Multistage cascade impactors
  • Pulmonary delivery
  • Three-dimensional culture
  • Two-dimensional culture

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

Cite this

Acosta, M. F., Muralidharan, P., Meenach, S. A., Hayes, D., Black, S. M., & Mansour, H. M. (2016). In vitro pulmonary cell culture in pharmaceutical inhalation aerosol delivery: 2-D, 3-D, and in situ bioimpactor models. Current Pharmaceutical Design, 22(17), 2522-2531.

In vitro pulmonary cell culture in pharmaceutical inhalation aerosol delivery : 2-D, 3-D, and in situ bioimpactor models. / Acosta, Maria F.; Muralidharan, Priya; Meenach, Samantha A.; Hayes, Don; Black, Stephen M.; Mansour, Heidi M.

In: Current Pharmaceutical Design, Vol. 22, No. 17, 01.05.2016, p. 2522-2531.

Research output: Contribution to journalArticle

Acosta, MF, Muralidharan, P, Meenach, SA, Hayes, D, Black, SM & Mansour, HM 2016, 'In vitro pulmonary cell culture in pharmaceutical inhalation aerosol delivery: 2-D, 3-D, and in situ bioimpactor models', Current Pharmaceutical Design, vol. 22, no. 17, pp. 2522-2531.
Acosta MF, Muralidharan P, Meenach SA, Hayes D, Black SM, Mansour HM. In vitro pulmonary cell culture in pharmaceutical inhalation aerosol delivery: 2-D, 3-D, and in situ bioimpactor models. Current Pharmaceutical Design. 2016 May 1;22(17):2522-2531.
Acosta, Maria F. ; Muralidharan, Priya ; Meenach, Samantha A. ; Hayes, Don ; Black, Stephen M. ; Mansour, Heidi M. / In vitro pulmonary cell culture in pharmaceutical inhalation aerosol delivery : 2-D, 3-D, and in situ bioimpactor models. In: Current Pharmaceutical Design. 2016 ; Vol. 22, No. 17. pp. 2522-2531.
@article{6190850580244336becd6ad4bf82a431,
title = "In vitro pulmonary cell culture in pharmaceutical inhalation aerosol delivery: 2-D, 3-D, and in situ bioimpactor models",
abstract = "Background: The use of non-invasive inhaled aerosols for pulmonary drug delivery continues to grow. This is due to the many unique advantages this delivery route offers for the treatment of both local and systemic diseases. The physicochemical properties of the formulated drugs as well as the physiology of the lungs play a key role in both the deposition and absorption of the particles. The airway and the alveolar epithelium are targets for the treatment of respiratory diseases. However, particles have to overcome biological barriers before they reach their target and produce an effect. Methods: In vitro aerosol dispersion performance (i.e. aerodynamic size and aerodynamic size distribution) of inhalable particles is quantified by inertial impaction, as required by regulatory agencies for an investigational pharmaceutical inhalation aerosol formulation to be approved for use in patients as a marketed pharmaceutical product. Using inertial impaction in conjunction with cell cultures of various pulmonary cells in situ as bioimpactors has unique aspects in correlating aerodynamic properties with pulmonary cellular behavior including viability and uptake. These can be as co-culture or in single culture, as 3-D multicellular spheroids or 2-D cellular monolayer using different conditions to grow them, such as air-liquid interface culture (ALI) or in liquid covered culture (LCC). Results: evaluation of the currently available in vitro models and the challenges in developing reliable cellular tools to predict the deposition of inhalable particles in the lungs as a function of aerodynamic particle properties is presented in the manuscript. Conclusion: The mechanistic aerodynamic and biophysical properties of inhaled aerosol particles on the entire respiratory tract at the cellular level based on aerodynamic size and aerodynamic size distribution will be better understood with the development of in vitro methods which are described in this work.",
keywords = "Aerosol deposition, Air-liquid interface (ALI) culture, Liquid covered culture (LCC), Lung cell culture, Multistage cascade impactors, Pulmonary delivery, Three-dimensional culture, Two-dimensional culture",
author = "Acosta, {Maria F.} and Priya Muralidharan and Meenach, {Samantha A.} and Don Hayes and Black, {Stephen M.} and Mansour, {Heidi M.}",
year = "2016",
month = "5",
day = "1",
language = "English (US)",
volume = "22",
pages = "2522--2531",
journal = "Current Pharmaceutical Design",
issn = "1381-6128",
publisher = "Bentham Science Publishers B.V.",
number = "17",

}

TY - JOUR

T1 - In vitro pulmonary cell culture in pharmaceutical inhalation aerosol delivery

T2 - 2-D, 3-D, and in situ bioimpactor models

AU - Acosta, Maria F.

AU - Muralidharan, Priya

AU - Meenach, Samantha A.

AU - Hayes, Don

AU - Black, Stephen M.

AU - Mansour, Heidi M.

PY - 2016/5/1

Y1 - 2016/5/1

N2 - Background: The use of non-invasive inhaled aerosols for pulmonary drug delivery continues to grow. This is due to the many unique advantages this delivery route offers for the treatment of both local and systemic diseases. The physicochemical properties of the formulated drugs as well as the physiology of the lungs play a key role in both the deposition and absorption of the particles. The airway and the alveolar epithelium are targets for the treatment of respiratory diseases. However, particles have to overcome biological barriers before they reach their target and produce an effect. Methods: In vitro aerosol dispersion performance (i.e. aerodynamic size and aerodynamic size distribution) of inhalable particles is quantified by inertial impaction, as required by regulatory agencies for an investigational pharmaceutical inhalation aerosol formulation to be approved for use in patients as a marketed pharmaceutical product. Using inertial impaction in conjunction with cell cultures of various pulmonary cells in situ as bioimpactors has unique aspects in correlating aerodynamic properties with pulmonary cellular behavior including viability and uptake. These can be as co-culture or in single culture, as 3-D multicellular spheroids or 2-D cellular monolayer using different conditions to grow them, such as air-liquid interface culture (ALI) or in liquid covered culture (LCC). Results: evaluation of the currently available in vitro models and the challenges in developing reliable cellular tools to predict the deposition of inhalable particles in the lungs as a function of aerodynamic particle properties is presented in the manuscript. Conclusion: The mechanistic aerodynamic and biophysical properties of inhaled aerosol particles on the entire respiratory tract at the cellular level based on aerodynamic size and aerodynamic size distribution will be better understood with the development of in vitro methods which are described in this work.

AB - Background: The use of non-invasive inhaled aerosols for pulmonary drug delivery continues to grow. This is due to the many unique advantages this delivery route offers for the treatment of both local and systemic diseases. The physicochemical properties of the formulated drugs as well as the physiology of the lungs play a key role in both the deposition and absorption of the particles. The airway and the alveolar epithelium are targets for the treatment of respiratory diseases. However, particles have to overcome biological barriers before they reach their target and produce an effect. Methods: In vitro aerosol dispersion performance (i.e. aerodynamic size and aerodynamic size distribution) of inhalable particles is quantified by inertial impaction, as required by regulatory agencies for an investigational pharmaceutical inhalation aerosol formulation to be approved for use in patients as a marketed pharmaceutical product. Using inertial impaction in conjunction with cell cultures of various pulmonary cells in situ as bioimpactors has unique aspects in correlating aerodynamic properties with pulmonary cellular behavior including viability and uptake. These can be as co-culture or in single culture, as 3-D multicellular spheroids or 2-D cellular monolayer using different conditions to grow them, such as air-liquid interface culture (ALI) or in liquid covered culture (LCC). Results: evaluation of the currently available in vitro models and the challenges in developing reliable cellular tools to predict the deposition of inhalable particles in the lungs as a function of aerodynamic particle properties is presented in the manuscript. Conclusion: The mechanistic aerodynamic and biophysical properties of inhaled aerosol particles on the entire respiratory tract at the cellular level based on aerodynamic size and aerodynamic size distribution will be better understood with the development of in vitro methods which are described in this work.

KW - Aerosol deposition

KW - Air-liquid interface (ALI) culture

KW - Liquid covered culture (LCC)

KW - Lung cell culture

KW - Multistage cascade impactors

KW - Pulmonary delivery

KW - Three-dimensional culture

KW - Two-dimensional culture

UR - http://www.scopus.com/inward/record.url?scp=84974688176&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84974688176&partnerID=8YFLogxK

M3 - Article

C2 - 26831643

AN - SCOPUS:84974688176

VL - 22

SP - 2522

EP - 2531

JO - Current Pharmaceutical Design

JF - Current Pharmaceutical Design

SN - 1381-6128

IS - 17

ER -