Abstract
Sustained and localized delivery of chemotherapeutics in postoperative cancer treatment leads to a radical improvement in prognosis and a much decreased risk of tumor recurrence. In this work, polydopamine (PDA)-coated superparamagnetic iron oxide nanoparticle (SPION)-loaded polycaprolactone and poly(lactic-co-glycolic acid) fibers were developed as a potential implant to ensure safe and sustained release of the chemotherapeutic drug methotrexate (MTX), as well as provide local contrast for magnetic resonance imaging (MRI). Fibres were prepared by co-axial electrospinning and loaded with MTX-layered double hydroxide (LDH) nanocomposites in the core, yielding organic–inorganic hybrids ranging from 1.23 to 1.48 µm in diameter. After surface coating with PDA, SPIONs were subsequently loaded on the fibre surface and found to be evenly distributed, providing high MRI contrast. In vitro drug release studies showed the PDA coated fibres gave sustained release of MTX over 18 days, and the release profile is responsive to conditions representative of the tumor microenvironment such as slightly acidic pH values or elevated concentrations of the reducing agent glutathione (GSH). In vitro studies with Caco-2 and A549 cells showed highly effective killing with the PDA coated formulations, which was further enhanced at higher levels of GSH. The fibres hence have the potential to act as an implantable drug-eluting platform for the sustained release of cytotoxic agents within a tumor site, providing a novel treatment option for post-operative cancer patients.
Original language | English |
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Article number | 121493 |
Number of pages | 13 |
Journal | International Journal of Pharmaceutics |
Volume | 615 |
Early online date | 19 Jan 2022 |
DOIs | |
Publication status | Published - 5 Mar 2022 |
Bibliographical note
Funding Information:FZ was supported by a NIHR UCLH Biomedical Research Centre (BRC) grant, UK-MRC ImagingBioPro grant (MR/R025673/1), the UCL Department of Medical Physics and Biomedical Engineering and the EPSRC (EP/M020533/1 ; CMIC Pump-Priming Award). Support from the Taishan Scholar Program of Shandong, China (tsqn201909100) to facilitate FZ's collaboration with JL is acknowledged.
Publisher Copyright:
© 2022 Elsevier B.V.
Keywords
- Cancer
- Electrospun nanofibres
- Implant
- Polydopamine
- Theranostic
ASJC Scopus subject areas
- Pharmaceutical Science