Assessment of chemical stability of monoclonal antibody and antibody drug conjugate administered by pressurized intraperitoneal aerosol chemotherapy

Article Article scientifique Article Assessment of chemical stability of monoclonal antibody and antibody drug conjugate administered by pressurized intraperitoneal aerosol chemotherapy eng 2024-08 2024-12 author D'Atri Valentina School of Pharmaceutical Sciences, University of Geneva, CMU, Rue Michel Servet 1, Geneva 1211, Switzerland; Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, CMU, Rue Michel Servet 1, Geneva 1211, Switzerland. 846921 author Galy Guillaume Pharmacy, Lausanne University Hospital (CHUV), Lausanne, Switzerland. author Buff Mathias 0009-0005-2338-8954 School of Pharmaceutical Sciences, University of Geneva, CMU, Rue Michel Servet 1, Geneva 1211, Switzerland; Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, CMU, Rue Michel Servet 1, Geneva 1211, Switzerland. 825407 Section des sciences pharmaceutiques (FARMA) Mathias Quentin Patrice Buff author Imiołek Mateusz Waters Corporation, Geneva 1211, Switzerland. author Hübner Martin Visceral Surgery, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), Switzerland. author Undurraga Manuela Division of Gynecology, Department of Pediatrics and Gynecology, Hôpitaux Universitaires de Genève, Genève, Switzerland. author Labidi-Galy Sana Intidhar Department of Oncology, Hôpitaux Universitaires de Genève, Genève, Switzerland; Faculty of Medicine, Department of Medicine and Center of Translational Research in Onco-Hematology, University of Geneva, Swiss Cancer Center Leman, Genève, Switzerland. 817058 Département de médecine (DEMED) author Guillarme Davy School of Pharmaceutical Sciences, University of Geneva, CMU, Rue Michel Servet 1, Geneva 1211, Switzerland; Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, CMU, Rue Michel Servet 1, Geneva 1211, Switzerland. Electronic address: davy.guillarme@unige.ch. 623637 Section des sciences pharmaceutiques (FARMA) author Carrez Laurent Pharmacy, Lausanne University Hospital (CHUV), Lausanne, Switzerland. 116410 10.1016/j.jpba.2024.116410 39173499 0731-7085 https://linkinghub.elsevier.com/retrieve/pii/S0731708524004503 Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new therapeutic approach for patients with peritoneal cancer. So far, most published studies investigated the administration of established cytostatic agents through PIPAC. This study aimed to evaluate the effect of PIPAC on two breakthrough anti-cancer agents, specifically anti-PD1 pembrolizumab, and anti-HER2 antibody-drug conjugate (ADC) - trastuzumab-deruxtecan. We conducted systematic analyses on samples of pembrolizumab and trastuzumab-deruxtecan at clinically relevant concentrations before and after PIPAC administration using an experimental setup of a hermetic container system, mimicking the abdominal cavity and using identical features as in clinical use. We utilized a range of chromatographic and spectroscopic techniques to explore potential alterations in the primary, secondary, and tertiary structures of the drugs, focusing on post-translational modifications resulting from the aerosolization. Our findings indicate that PIPAC did not compromise the integrity of tested biopharmaceuticals. The size variants of both drugs, assessed by size exclusion chromatography (SEC), remained unchanged. Reversed-phase liquid chromatography (RPLC) and hydrophobic interaction chromatography (HIC) revealed no significant differences in hydrophobicity variants, the average drug-to-antibody ratio (DAR), or DAR distribution before and after PIPAC treatment. Circular dichroism (CD) spectroscopy confirmed that the secondary and tertiary structures were preserved. While pembrolizumab showed no change in charge variants post-PIPAC, trastuzumab-deruxtecan exhibited a non-negligible change in the quantity of charge variants on the monoclonal antibody itself, while the payload remained unchanged. This shift could possibly be related to the metallic composition of the CapnoPen® device (made of nickel and chromium) used in PIPAC and for these experiments. Together, our results suggest that PIPAC does not alter the structure of pembrolizumab and trastuzumab-deruxtecan, paving the way for future clinical trials. PIPAC Pembrolizumab Keytruda® Pressurized intra-peritoneal aerosol chemotherapy Stability Trastuzumab-deruxtecan enhertu® Antibody drug conjugate Drug to antibody ratio Dewey 615 Dewey 618 31 Section des sciences pharmaceutiques 17 58 Département de pédiatrie, gynécologie et obstétrique 223 false 881 Sciences analytiques https://doi.org/10.1016/j.jpba.2024.116410 Journal of pharmaceutical and biomedical analysis 251 4a467e4d-6880-4dc9-87d4-e276cbdd9aa9 Article (Published version) Public JPharmBMA-Assessment-stability-anti.pdf 4172774 application/pdf CC BY-4.0 44c081b4bf668012e4be00fae65a1be279e0a3ab136fcd41e218832d52ff4380 a045b551-8973-44ab-9425-176f45cd71df Supplemental data Public JPharmBMA-Assessment-stability-anti.pptx 260079 application/vnd.openxmlformats-officedocument.presentationml.presentation CC BY-4.0 c2a72b490e69dc0fa4953e4e761c9efc282b11edcab54d70c5fca89cb0577b15 openAccess Faculté des sciences / Section des sciences pharmaceutiques Faculté de médecine / Section de médecine clinique / Département de pédiatrie, gynécologie et obstétrique

Title	Published in	Year	Views	Downloads

Assessment of chemical stability of monoclonal antibody and antibody drug conjugate administered by pressurized intraperitoneal aerosol chemotherapy	Journal of pharmaceutical and biomedical analysis	2024	11	6
Effect of the nonspecific binding in differential impedance biosensing	Biointerphases	2019	277	251

Archive ouverte UNIGE

Buff, Mathias Quentin Patrice

account_balance Affiliation entities

Research groups

Affiliation entities