Drug delivery of 6-bromoindirubin-3’-glycerol-oxime ether employing poly(d,l-lactide-co-glycolide)-based nanoencapsulation techniques with sustainable solvents

Czapka, Anna; Grune, Christian; Schädel, Patrick; Bachmann, Vivien; Scheuer, Karl; Dirauf, Michael; Weber, Christine; Skaltsounis, Alexios-Leandros; Jandt, Klaus D.; Schubert, Ulrich S.; Fischer, Dagmar; Werz, Oliver

Abstract:

Insufficient solubility and stability of bioactive small molecules as well as poor biocompatibility may cause low bioavailability and are common obstacles in drug development. One example of such problematic molecules is 6-bromoindirubin-3'-glycerol-oxime ether (6BIGOE), a hydrophobic indirubin derivative. 6BIGOE potently modulates the release of inflammatory cytokines and lipid mediators from isolated human monocytes through inhibition of glycogen synthase kinase-3 in a favorable fashion. However, 6BIGOE suffers from poor solubility and short half-lives in biological aqueous environment and exerts cytotoxic effects in various mammalian cells. In order to overcome the poor water solubility, instability and cytotoxicity of 6BIGOE, we applied encapsulation into poly(d,l-lactide-co-glycolide) (PLGA)-based nanoparticles by employing formulation methods using the sustainable solvents Cyrene™ or 400 g/mol poly(ethylene glycol) as suitable technology for efficient drug delivery of 6BIGOE.

Year:

2022

Type of Publication:

Article

Journal:

Journal of Nanobiotechnology

Volume:

20

Pages:

5

DOI:

https://doi.org/10.1186/s12951-021-01179-7