Controlling the function of bioactive worm micelles by enzyme-cleavable non-covalent inter-assembly cross-linking.

Autor: Romanovska A; Biomaterials and Polymer Science, Department of Bio- and Chemical Engineering, TU Dortmund, Emil-Figge-Straße 66, 44227 Dortmund, Germany., Schmidt M; Biomaterials and Polymer Science, Department of Bio- and Chemical Engineering, TU Dortmund, Emil-Figge-Straße 66, 44227 Dortmund, Germany., Brandt V; Biomaterials and Polymer Science, Department of Bio- and Chemical Engineering, TU Dortmund, Emil-Figge-Straße 66, 44227 Dortmund, Germany., Tophoven J; Biomaterials and Polymer Science, Department of Bio- and Chemical Engineering, TU Dortmund, Emil-Figge-Straße 66, 44227 Dortmund, Germany., Tiller JC; Biomaterials and Polymer Science, Department of Bio- and Chemical Engineering, TU Dortmund, Emil-Figge-Straße 66, 44227 Dortmund, Germany. Electronic address: joerg.tiller@udo.edu.
Jazyk: angličtina
Zdroj: Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2024 Apr; Vol. 368, pp. 15-23. Date of Electronic Publication: 2024 Feb 21.
DOI: 10.1016/j.jconrel.2024.02.013
Abstrakt: Drugs that form self-assembled supramolecular structures to be most-active is a promising way of creating new highly specific and active pharmaceuticals. Controlling the activity of bioactive supramolecular structures such as drug-loaded micelles is possible by both core/shell and inter-assembly cross-linking. However, if the flexibility of the assembly is mandatory for the activity cross-linking is not feasible. Thus, such structures cannot be manipulated in their activity. The present study demonstrates a novel concept to control the activity of not drug-releasing, non-cross-linked bioactive superstructures. This is achieved by formation of nanostructured nanoparticles derived by non-covalent inter-assembly cross-linking of the superstructures. This is shown on the example of amphiphilic diblock-copolymers conjugated with the antibiotic ciprofloxacin (CIP). These polymer-antibiotic conjugates form worm micelles, which greatly activate the conjugated antibiotic without releasing it. Non-covalent inter-assembly cross-linking of these CIP-worm-micelles with amphiphilic triblock copolymers terminated with lipase-cleavable esters leads to nanostructured nanoparticles that resemble cross-linked worm micelles and show an up to 135-fold lower activity than the free worm micelles. The activity of the worm-micelles can be fully recovered by cleaving the end groups of the polymeric cross-linker with lipase.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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