Cavitation-induced release of liposomal chemotherapy in orthotopic murine pancreatic cancer models: A feasibility study - 08/11/19
, Ariane Vienne a, Jean-Louis Mestas c, Carlos Pratico a, d, Carole Nicco a, d, Christiane Chereau a, d, Jean-Martial Marie c, Alexei Moussatov c, Gilles Renault a, d, Frederic Batteux a, d, Cyril Lafon c, Frederic Prat a, dBienvenue sur EM-consulte, la référence des professionnels de santé.
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| pages | 13 |
| Iconographies | 7 |
| Vidéos | 0 |
| Autres | 0 |
Highlights |
• | Pancreatic ductal adenocarcinoma, one of the most dreadful malignancies, is rapidly increasing in incidence. |
• | Ultrasound has the potential to trigger release in a well-defined volume of tissue by fine-focusing the US beam and creating local cavitation, thus increasing the therapeutic-toxicity ratio of encapsulated drugs in a specific target tissue. |
• | This study demonstrates the feasibility of applying inertial cavitation in addition to drug-carrying liposomes accumulated in the tumor. |
• | Even if this study has several limitations, we brought preliminary data to demonstrate that inertial cavitation could be generated to increase the therapeutic effect of drug-carrying liposomes accumulated in the tumor. |
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.
Le texte complet de cet article est disponible en PDF.Keywords : Ultrasound, Drug delivery, Liposome, Cavitation, Chemoresistance, Pancreatic cancer
Plan
Vol 43 - N° 6
P. 669-681 - novembre 2019 Retour au numéro
Article précédent
- Characteristic and outcomes of patients with pathologic complete response after preoperative treatment in borderline and locally advanced pancreatic adenocarcinoma: An AGEO multicentric retrospective cohort
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