1. Cavitation-induced release of liposomal chemotherapy in orthotopic murine pancreatic cancer models: A feasibility study
- Author
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Cyril Lafon, Gilles Renault, Jean-Martial Marie, Frédéric Prat, Christiane Chéreau, Alexei Moussatov, Jean-Louis Mestas, Carlos Alberto Pratico, Carole Nicco, Marine Camus, Frédéric Batteux, Ariane Vienne, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Application des ultrasons à la thérapie (LabTAU), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and CCSD, Accord Elsevier
- Subjects
Male ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,Mice, Nude ,Polyethylene Glycols ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Nude mouse ,Drug Delivery Systems ,Pharmacokinetics ,In vivo ,Pancreatic cancer ,medicine ,Animals ,Ultrasonography ,Chemotherapy ,Antibiotics, Antineoplastic ,Hepatology ,biology ,business.industry ,Ultrasound ,Gastroenterology ,medicine.disease ,biology.organism_classification ,Gemcitabine ,3. Good health ,Rats ,Pancreatic Neoplasms ,[SDV] Life Sciences [q-bio] ,Disease Models, Animal ,Doxorubicin ,Rats, Inbred Lew ,030220 oncology & carcinogenesis ,Drug delivery ,Liposomes ,Cancer research ,Feasibility Studies ,030211 gastroenterology & hepatology ,Female ,business ,medicine.drug - Abstract
Summary Targeted and triggered release of liposomal drug using ultrasound (US) induced cavitation represents a promising treatment modality to increase the therapeutic-toxicity ratio of encapsulated chemotherapy. Objectives To study the feasibility and efficacy of a combination of focused US and liposomal doxorubicin (US-L-DOX) release in orthotopic murine models of pancreatic cancer. Material and methods A confocal US setup was developed to generate US inertial cavitation delivery in a controlled and reproducible manner and designed for two distinct murine orthotopic pancreatic cancer models. Controlled cavitation at 1 MHz was applied within the tumors after L-DOX injection according to a preliminary pharmacokinetic study. Results In vitro studies confirmed that L-DOX was cytostatic. In vivo pharmacokinetic study showed L-DOX peak tumor accumulation at 48h. Feasibility of L-DOX injection and US delivery was demonstrated in both murine models. In a nude mouse model, at W9 after implantation (W5 after treatment), US-L-DOX group (median [IQR] 51.43 mm3 [35.1–871.95]) exhibited significantly lower tumor volumes than the sham group (216.28 [96.12–1202.92]), the US group (359.44 [131.48–1649.25]), and the L-DOX group (255.94 [84.09–943.72]), and a trend, although not statistically significant, to a lower volume than Gemcitabine group (90.48 [42.14–367.78]). Conclusion This study demonstrates that inertial cavitation can be generated to increase the therapeutic effect of drug-carrying liposomes accumulated in the tumor. This approach is potentially an important step towards a therapeutic application of cavitation-induced drug delivery in pancreatic cancer.
- Published
- 2019
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