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The feasibility of Pressurised Intraperitoneal Aerosolised Virotherapy (PIPAV) to administer oncolytic adenoviruses

Tate, Sophia J., Van de Sande, Leen, Ceelen, Wim P., Torkington, Jared and Parker, Alan L. ORCID: https://orcid.org/0000-0002-9302-1761 2021. The feasibility of Pressurised Intraperitoneal Aerosolised Virotherapy (PIPAV) to administer oncolytic adenoviruses. Pharmaceutics 13 (12) , 2043. 10.3390/pharmaceutics13122043

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Abstract

Background: The prognosis of patients with peritoneal metastases is poor. Treatment options are limited because systemically delivered chemotherapy is not usually effective in this type of disease. Pressurised intraperitoneal aerosolised chemotherapy (PIPAC) is a recently developed alternative technology for delivering intraperitoneal chemotherapy, potentially enhancing treatment efficacy. Here, we assess the feasibility of pressurised intraperitoneal aerosolised virotherapy (PIPAV) to deliver a different class of anticancer agents, oncolytic adenoviruses, in vitro and in vivo. Methods: Adenoviral vectors expressing reporter genes green fluorescence protein (Ad5.GFP) or firefly luciferase (Ad5.Luc) were subject to pressurised aerosolisation. The ability of the virus to survive PIPAV was assessed in vitro and in vivo by monitoring reporter gene activity. Wistar rats subjected to PIPAV were assessed for any adverse procedure related events. Results: In vitro transduction assays demonstrated that Ad5 retained viability following pressurised aerosolisation and could transduce permissive cells equally effectively as non-aerosolised control vector. PIPAV was well tolerated in rats, although minimal transduction was observed following intraperitoneal administration. Conclusions: PIPAV appears viable and well tolerated, though in vivo efficacy requires further optimisation.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: MDPI
ISSN: 1999-4923
Funders: Wellcome Trust
Date of First Compliant Deposit: 1 December 2021
Date of Acceptance: 25 November 2021
Last Modified: 07 May 2023 14:27
URI: https://orca.cardiff.ac.uk/id/eprint/145857

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