Publikationsdatenbank

Design and testing of efficient mucus-penetrating nanogels:
pitfalls of preclinical testing and lessons learned (2021)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Charbaji, Rawan

Kar, Mrityunjoy

Theune, Loryn E.

Bergueiro, Julián

Eichhorst, Anne

Navarro, Lucila

Graff, Patrick

Stumpff, Friederike (WE 2)

Calderón, Marcelo

Hedtrich, Sarah

Quelle

Small : nano micro

Bandzählung: 17

Heftzählung: 23

Seiten: Artikel 2007963

ISSN: 1613-6829

Sprache

Englisch

Verweise

URL (Volltext): https://onlinelibrary.wiley.com/doi/10.1002/smll.202007963

DOI: 10.1002/smll.202007963

Pubmed: 33719187

Kontakt

Institut für Veterinär-Physiologie

Oertzenweg 19 b
14163 Berlin
+49 30 838 62600
physiologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Mucosal surfaces pose a challenging environment for efficient drug delivery. Various delivery strategies such as nanoparticles have been employed so far; yet, still yielding limited success. To address the need of efficient transmucosal drug delivery, this report presents the synthesis of novel disulfide-containing dendritic polyglycerol (dPG)-based nanogels and their preclinical testing. A bifunctional disulfide-containing linker is coupled to dPG to act as a macromolecular crosslinker for poly-N-isopropylacrylamide (PNIPAM) and poly-N-isopropylmethacrylamide (PNIPMAM) in a precipitation polymerization process. A systematic analysis of the polymerization reveals the importance of a careful polymer choice to yield mucus-degradable nanogels with diameters between 100 and 200 nm, low polydispersity, and intact disulfide linkers. Absorption studies in porcine intestinal tissue and human bronchial epithelial models demonstrate that disulfide-containing nanogels are highly efficient in overcoming mucosal barriers. The nanogels efficiently degrade and deliver the anti-inflammatory biomacromolecule etanercept into epithelial tissues yielding local anti-inflammatory effects. Over the course of this work, several problems are encountered due to a limited availability of valid test systems for mucosal drug-delivery systems. Hence, this study also emphasizes how critical a combined and multifaceted approach is for the preclinical testing of mucosal drug-delivery systems, discusses potential pitfalls, and provides suggestions for solutions.