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Open Access Green as soon as Postprint is submitted to ZB.
Biokinetics of aerosolized liposomal ciclosporin A in human lung cells in vitro using an air-liquid cell interface exposure system.
J. Aerosol Med. Pulm. Drug Deliv. 30, 411-424 (2017)
Background: Inhalation of aerosolized drugs is a promising route for noninvasive targeted drug delivery to the lung. Nanocarrier systems such as liposomes have been explored for inhalation therapy opening new avenues, including stabilization of nonsoluble drugs (e.g., Ciclosporin A [CsA]) and controlled release. Methods: The biokinetic behavior of the immunosuppressive drug CsA encapsulated in liposomes (L-CsA) at the lung epithelial barrier was studied in vitro. Human lung epithelial cells (alveolar A549 and bronchial 16HBE14o- epithelial cells) were exposed to aerosolized L-CsA at the air-liquid interface (ALI) using a dose-controlled air-liquid interface cell exposure (ALICE) system and the temporal profile of the L-CsA dose in the apical, basal, and cell compartment was monitored up to 24 hours. Results: Aerosolization of different volumes of L-CsA solution with the ALICE resulted in dose-controlled, spatially uniform, and reproducible L-CsA delivery. Cell viability at 24 hours postexposure was not impaired and immunofluorescence staining revealed the typical epithelial cell morphology in control as well as in L-CsA-exposed cells. The (pro-)inflammatory interleukin-8 levels were not elevated under any condition. The biokinetic analysis revealed that both cell types formed a tight, but imperfect, barrier for L-CsA resulting in initially high transbarrier L-CsA transport rates, which ceased after about 4 hours. Although substantial transbarrier L-CsA transport was observed for both cell types, respectively, a 150-fold higher L-CsA concentration was established in the apical and cell compared to the basal compartment. Most importantly, for pulmonary drug targeting, a high cellular L-CsA dose level (20%-25% of the delivered dose) was obtained rapidly (<1 hour) and maintained for at least 24 hours. Conclusions: The ALICE system combined with lung epithelial cells cultured at the ALI offers a reliable and relevant in vitro platform technology to study the effects of inhalable substances such as L-CsA under biomimetic conditions.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Aerosolized Liposomes ; Air-liquid Exposures ; Biokinetics ; Ciclosporin A ; Lung Cell Cultures; Drug-delivery; Particle-size; Inhaled Corticosteroids; Nanoparticle Toxicity; Inhalation Solution; Gold Nanoparticles; Propylene-glycol; Epithelial-cells; Culture Models; Transplantation
ISSN (print) / ISBN
0894-2684
e-ISSN
1557-9026
Quellenangaben
Volume: 30,
Issue: 6,
Pages: 411-424
Publisher
Mary Ann Liebert
Publishing Place
New Rochelle
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Lung Health and Immunity (LHI)