Pulmonary and renal tolerance of cisplatin-based regimens combining intravenous and endotracheal routes for lung cancer treatment in mice.

Autor: Chraibi S; Unit of Pharmaceutics and Biopharmaceutics, Faculty of Pharmacy, Université libre de Bruxelles (ULB), Brussels, Belgium. Electronic address: selma.chraibi@ulb.be., Rosière R; Unit of Pharmaceutics and Biopharmaceutics, Faculty of Pharmacy, Université libre de Bruxelles (ULB), Brussels, Belgium; InhaTarget Therapeutics, Rue Auguste Piccard 37, Gosselies, Belgium., De Prez E; Laboratory of Experimental Nephrology, Faculty of Medicine, ULB, Brussels, Belgium., Antoine MH; Laboratory of Experimental Nephrology, Faculty of Medicine, ULB, Brussels, Belgium., Remmelink M; Department of Pathology, ULB, Hôpital Erasme, Brussels, Belgium., Langer I; Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), ULB, Brussels, Belgium., Nortier J; Laboratory of Experimental Nephrology, Faculty of Medicine, ULB, Brussels, Belgium., Amighi K; Unit of Pharmaceutics and Biopharmaceutics, Faculty of Pharmacy, Université libre de Bruxelles (ULB), Brussels, Belgium., Wauthoz N; Unit of Pharmaceutics and Biopharmaceutics, Faculty of Pharmacy, Université libre de Bruxelles (ULB), Brussels, Belgium.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2021 Apr 15; Vol. 599, pp. 120425. Date of Electronic Publication: 2021 Feb 27.
DOI: 10.1016/j.ijpharm.2021.120425
Abstrakt: Despite recent advances, platinum-based chemotherapy (partially composed of cisplatin, CIS) remains the backbone of non-small-cell lung cancer treatment. As CIS presents a cumulative and dose-limiting nephrotoxicity, it is currently administered with an interruption phase of 3-4 weeks between treatment cycles. During these periods, the patient recovers from the treatment side effects but so does the tumour. Our strategy is to increase the treatment frequency by delivering a cisplatin controlled-release dry powder for inhalation (CIS-DPI) formulation during these off-cycles to expose the tumour environment for longer to CIS, increasing its effectiveness. This is promising as long as the pulmonary and renal toxicities remain acceptable. The aim of the present investigation was to evaluate the pulmonary and renal tolerance of CIS-DPI (three times per cycle) and CIS using the intravenous (IV) route (CIS-IV) (one time per cycle) as monotherapies and to optimize their combination in terms of dose and schedule. At the maximum tolerated dose (MTD), combining CIS-DPI and CIS-IV impaired the pulmonary and the renal tolerance. Therefore, pulmonary tolerance was improved when the CIS-IV dose was decreased by 25% (to 1.5 mg/kg) while maintaining the MTD for CIS-DPI. In addition to this dose adjustment, a delay of 24 h between CIS-DPI and CIS-IV administrations limited the acute kidney injury.
(Copyright © 2021 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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