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Röhm, M.* ; Carle, S.* ; Maigler, F.* ; Flamm, J.* ; Kramer, V.* ; Mavoungou, C.* ; Schmid, O. ; Schindowski, K.*

A comprehensive screening platform for aerosolizable protein formulations for intranasal and pulmonary drug delivery.

Int. J. Pharm. 532, 537-546 (2017)
Postprint Forschungsdaten DOI PMC
Open Access Green
Aerosolized administration of biopharmaceuticals to the airways is a promising route for nasal and pulmonary drug delivery, but - in contrast to small molecules - little is known about the effects of aerosolization on safety and efficacy of biopharmaceuticals. Proteins are sensitive against aerosolization-associated shear stress. Tailored formulations can shield proteins and enhance permeation, but formulation development requires extensive screening approaches. Thus, the aim of this study was to develop a cell-based in vitro technology platform that includes screening of protein quality after aerosolization and transepithelial permeation. For efficient screening, a previously published aerosolization-surrogate assay was used in a design of experiments approach to screen suitable formulations for an IgG and an antigen-binding fragment (Fab) as exemplary biopharmaceuticals. Efficient, dose-controlled aerosol-cell delivery was performed with the ALICE-CLOUD system containing RPMI 2650 epithelial cells at the air-liquid interface. We could demonstrate that our technology platform allows for rapid and efficient screening of formulations consisting of different excipients (here: arginine, cyclodextrin, polysorbate, sorbitol, and trehalose) to minimize aerosolization-induced protein aggregation and maximize permeation through an in vitro epithelial cell barrier. Formulations reduced aggregation of native Fab and IgG relative to vehicle up to 50% and enhanced transepithelial permeation rate up to 2.8-fold.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Antibodies ; Aerosolization ; Aggregation ; Air-liquid Interface ; Airways ; Nebulizer ; Permeation ; Scaffolds ; Stability; Air-liquid Interface; Immunoglobulin Transport Pathway; Hydroxypropyl-beta-cyclodextrin; Neonatal Fc-receptor; Tumor-cell Line; Insulin-receptor; In-vitro; Cognitive Impairment; Diploid Karyotype; Epithelial-cells
Sprache
Veröffentlichungsjahr 2017
HGF-Berichtsjahr 2017
ISSN (print) / ISBN 0378-5173
e-ISSN 1873-3476
Zeitschrift International Journal of Pharmaceutics
Quellenangaben Band: 532, Heft: 1, Seiten: 537-546 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort Amsterdam
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Lung Health and Immunity (LHI)
POF Topic(s) 30202 - Environmental Health
Forschungsfeld(er) Lung Research
PSP-Element(e) G-505000-008
DOI 10.1016/j.ijpharm.2017.09.027
WOS ID WOS:000413669700055
Scopus ID 85029714379
PubMed ID 28917988
Erfassungsdatum 2017-09-25
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