Structural Investigation on How Guest Loading of Poly(2-oxazoline)-Based Micelles Affects the Interaction with Simulated Intestinal Fluids.
ACS Biomater Sci Eng
; 9(8): 4821-4830, 2023 08 14.
Article
en En
| MEDLINE
| ID: mdl-37441793
ABSTRACT
Drug loading of polymer micelles can have a profound effect on their particle size and morphology as well as their physicochemical properties. In turn, this influences performance in biological environments. For oral delivery of drugs, the intestinal environment is key, and consequently, a thorough structural understanding of what happens at this material-biology interface is required to understand in vivo performance and tailor improved delivery vehicles. In this study, we address this interface in vitro through a detailed structural characterization of the colloidal assemblies of polymeric micelles based on poly(2-oxazolines) with three different guest loadings with the natural product curcumin (17-52 wt %) in fed-state simulated intestinal fluids (FeSSIF). For this, we employ NMR spectroscopy, in particular, 1H NMR, 1H-1H-NOESY, and 1H DOSY experiments complemented by quantum chemical calculations and cryo-TEM measurements. Through this mixture of methods, we identified curcumin-taurocholate interactions as central interaction patterns alongside interactions with the polymer and lipids. Furthermore, curcumin molecules can be exchanged between polymer micelles and bile colloids, an important prerequisite for their uptake. Finally, increased loading of the polymer micelles with curcumin resulted in a larger number of vesicles as taurocholateâthrough coordination with Curâis less available to form nanoparticles with the lipids. The loading-dependent behavior found in this study deviates from previous work on a different drug substance highlighting the need for further studies including different drug molecules and polymer types to improve the understanding of events on the molecular level.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Curcumina
/
Antineoplásicos
Idioma:
En
Revista:
ACS Biomater Sci Eng
Año:
2023
Tipo del documento:
Article
País de afiliación:
Alemania