A PEGylated liposomal formulation of prochlorperazine that limits brain exposure but retains dynamin II activity: A potential adjuvant therapy for cancer patients receiving chemotherapeutic mAbs.

Autor: Subasic CN; School of Biomedical Sciences, University of Queensland, St Lucia, QLD 4072, Australia., Simpson F; Frazer Institute, University of Queensland, St Lucia, QLD 4072, Australia., Minchin RF; School of Biomedical Sciences, University of Queensland, St Lucia, QLD 4072, Australia., Kaminskas LM; School of Biomedical Sciences, University of Queensland, St Lucia, QLD 4072, Australia. Electronic address: l.kaminskas@uq.edu.au.
Jazyk: angličtina
Zdroj: Nanomedicine : nanotechnology, biology, and medicine [Nanomedicine] 2024 Feb; Vol. 56, pp. 102733. Date of Electronic Publication: 2024 Jan 08.
DOI: 10.1016/j.nano.2024.102733
Abstrakt: Anti-cancer monoclonal antibodies often fail to provide therapeutic benefit in receptor-positive patients due to rapid endocytosis of antibody-bound cell surface receptors. High dose co-administration of prochlorperazine (PCZ) inhibits endocytosis and sensitises tumours to mAbs by inhibiting dynamin II but can also introduce neurological side effects. We examined the potential to use PEGylated liposomal formulations of PCZ (LPCZ) to retain the anti-cancer effects of PCZ, but limit brain uptake. Uncharged liposomes showed complete drug encapsulation and pH-dependent drug release, but cationic liposomes showed limited drug encapsulation and lacked pH-dependent drug release. Uncharged LPCZ showed comparable inhibition of EGFR internalisation to free PCZ in KJD cells. After IV administration to rats, LPCZ reduced the plasma clearance and brain uptake of PCZ compared to IV PCZ. The results suggest that LPCZ may offer some benefit over PCZ as an adjunct therapy in cancer patients receiving mAb treatment.
Competing Interests: Declaration of competing interest F.S. holds several patents relevant to the field: PAT-02100-JP-01; 2015-538212; 02100-GB-01; 13848409.2; 02100-DE-01; 60 2013059561.5; 02100-AU-02; 2013334493; 02100-US-01 14/438440; 02100-JP-01 2015-538212. F.S. declares that she completed a 2019 contract with Merck (published as part of her group's work in Cell 2020) and has presented at a conference sponsored by Telix. No conflict of interest by the other authors.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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