Wormlike nanovector with enhanced drug loading using blends of biodegradable block copolymers

Roxane Ridolfo, Jeanrick J. Arends, Jan C.M. van Hest (Corresponding author), David S. Williams

Research output: Contribution to journalArticleAcademic

11 Citations (Scopus)

Abstract

The application of nanoparticles comprising amphiphilic block copolymers for the delivery of drugs is a subject of great interest as they hold promise for more effective and selective therapies. In order to achieve this ambition, it is of critical importance to develop our understanding of the self-assembly mechanisms by which block copolymers undergo so that we can control their morphology, tune their ability to be loaded with biofunctional cargoes, and optimize their interactions with target cells. To this end, we have developed a strategy by which blends of (biocompatible) amphiphilic block copolymers generate nonspherical nanovectors, simultaneously enhancing drug loading without the need for subsequent purification owing to the use of the biocompatible direct hydration approach. The principal morphology achieved using this blending strategy are wormlike nanovectors (nanoworms, NWs), with an elongated form known to have a profound effect on flow behavior and interactions with cells. Unloaded nanoworms are not toxic toward human retinal (ARPE-19) cells and can be effectively endocytosed even after varying the surface charge. In terms of drug loading, we demonstrate that uptake of dexamethasone (DEX; a clinically relevant therapeutic agent) in nanoworms (DEX@NWs) can be enhanced using this process, increasing drug content up to 0.5 mg/mL (10 wt % in particles). Furthermore, such nanoworms are stable for at least 5 months and are, therefore, a promising platform for nanomedicine applications.

Original languageEnglish
Pages (from-to)2199-2207
Number of pages9
JournalBiomacromolecules
Volume21
Issue number6
Early online date8 Apr 2020
DOIs
Publication statusPublished - 8 Jun 2020

Funding

The authors would like to thank Vijayabhaskarreddy Junnuthula, Shirin Tavakoli, and Arto Urtti for assistance with cell studies. We also thank Imke Welzen-Pijpers and Alexander Mason for CryoTEM measurements. We thank the European Union’s Horizon 2020 research and innovation programme Marie Sklodowska-Curie Innovative Training Networks Nanomed (no. 676137) for funding. We thank the Ser Cymru II programme for support of DSW; this project received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 663830.

FundersFunder number
Horizon 2020 Framework Programme663830, 676137

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