Estimation of endotoxin level in nanocrystal dispersion of DK-I-56-1 intended for parenteral administration
Конференцијски прилог (Објављена верзија)
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Estimation of endotoxin level in nanocrystal dispersion of DK-I-56-1 intended for parenteral administration
Jelena Mitrović1, Tanja Ilić1, Ivan Jančić2, Biljana Bufan2, Miroslav Savić3, Snežana Savić1
1 Department of Pharmaceutical Technology and Cosmetology, University of Belgrade – Faculty of Pharmacy, Vojvode Stepe 450, 11000 Belgrade, Serbia
2 Department of Microbiology and Immunology, University of Belgrade – Faculty of Pharmacy, Vojvode Stepe 450, 11000 Belgrade, Serbia
3 Department of Pharmacology, University of Belgrade – Faculty of Pharmacy, Vojvode Stepe 450, 11000 Belgrade, Serbia
Estimation of endotoxin level in parenteral formulations is a prerequisite for numerous in vitro tests in preclinical studies and for future clinical development. However, the Limulus amoebocyte lysate (LAL) test in formulations containing nanoparticles could often lead to misinterpretation of results. Therefore, we tested if endotoxins could be detected in nanocrystal dispersions by the comme...rcial gel clot assay kit. Nanocrystals of DK-I-56-1 (7‑methoxy‑2-(4‑methoxy‑d3-phenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one) were prepared by wet-ball milling, lyophilized and reconstituted with water for injection prior experiment. Different dilutions of nanocrystal dispersion in LAL reagent water were prepared as well as positive and negative control. Despite difficulties to detect gel clots, they were visible in the sample at dilutions 1:75 and below. According to the protocol, the endotoxin limit was estimated to be 25.00 EU/ml, which corresponds to <12.50 EU/mg of DK-I-56-1. This value relates to the endotoxin limit for diazepam, with the similar dosing regimen as proposed for DK-I-56-1.
Кључне речи:
nanocrystals / pyrazoloquinolinones / lyophilization / endotoxin / parenteral administrationИзвор:
NANOGVA Symposium, October 5th - 6th, 2023, Geneva, Switzerland, 2023Финансирање / пројекти:
- NanoCellEmoCog - Neuroimmune aspects of mood, anxiety and cognitive effects of leads/drug candidates acting at GABAA and/or sigma-2 receptors: In vitro/in vivo delineation by nano- and hiPSC-based platform (RS-ScienceFundRS-Ideje-7749108)
Институција/група
PharmacyTY - CONF AU - Mitrović, Jelena AU - Ilić, Tanja AU - Jančić, Ivan AU - Bufan, Biljana AU - Savić, Miroslav AU - Savić, Snežana PY - 2023 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5090 AB - Estimation of endotoxin level in nanocrystal dispersion of DK-I-56-1 intended for parenteral administration Jelena Mitrović1, Tanja Ilić1, Ivan Jančić2, Biljana Bufan2, Miroslav Savić3, Snežana Savić1 1 Department of Pharmaceutical Technology and Cosmetology, University of Belgrade – Faculty of Pharmacy, Vojvode Stepe 450, 11000 Belgrade, Serbia 2 Department of Microbiology and Immunology, University of Belgrade – Faculty of Pharmacy, Vojvode Stepe 450, 11000 Belgrade, Serbia 3 Department of Pharmacology, University of Belgrade – Faculty of Pharmacy, Vojvode Stepe 450, 11000 Belgrade, Serbia Estimation of endotoxin level in parenteral formulations is a prerequisite for numerous in vitro tests in preclinical studies and for future clinical development. However, the Limulus amoebocyte lysate (LAL) test in formulations containing nanoparticles could often lead to misinterpretation of results. Therefore, we tested if endotoxins could be detected in nanocrystal dispersions by the commercial gel clot assay kit. Nanocrystals of DK-I-56-1 (7‑methoxy‑2-(4‑methoxy‑d3-phenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one) were prepared by wet-ball milling, lyophilized and reconstituted with water for injection prior experiment. Different dilutions of nanocrystal dispersion in LAL reagent water were prepared as well as positive and negative control. Despite difficulties to detect gel clots, they were visible in the sample at dilutions 1:75 and below. According to the protocol, the endotoxin limit was estimated to be 25.00 EU/ml, which corresponds to <12.50 EU/mg of DK-I-56-1. This value relates to the endotoxin limit for diazepam, with the similar dosing regimen as proposed for DK-I-56-1. C3 - NANOGVA Symposium, October 5th - 6th, 2023, Geneva, Switzerland T1 - Estimation of endotoxin level in nanocrystal dispersion of DK-I-56-1 intended for parenteral administration UR - https://hdl.handle.net/21.15107/rcub_farfar_5090 ER -
@conference{ author = "Mitrović, Jelena and Ilić, Tanja and Jančić, Ivan and Bufan, Biljana and Savić, Miroslav and Savić, Snežana", year = "2023", abstract = "Estimation of endotoxin level in nanocrystal dispersion of DK-I-56-1 intended for parenteral administration Jelena Mitrović1, Tanja Ilić1, Ivan Jančić2, Biljana Bufan2, Miroslav Savić3, Snežana Savić1 1 Department of Pharmaceutical Technology and Cosmetology, University of Belgrade – Faculty of Pharmacy, Vojvode Stepe 450, 11000 Belgrade, Serbia 2 Department of Microbiology and Immunology, University of Belgrade – Faculty of Pharmacy, Vojvode Stepe 450, 11000 Belgrade, Serbia 3 Department of Pharmacology, University of Belgrade – Faculty of Pharmacy, Vojvode Stepe 450, 11000 Belgrade, Serbia Estimation of endotoxin level in parenteral formulations is a prerequisite for numerous in vitro tests in preclinical studies and for future clinical development. However, the Limulus amoebocyte lysate (LAL) test in formulations containing nanoparticles could often lead to misinterpretation of results. Therefore, we tested if endotoxins could be detected in nanocrystal dispersions by the commercial gel clot assay kit. Nanocrystals of DK-I-56-1 (7‑methoxy‑2-(4‑methoxy‑d3-phenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one) were prepared by wet-ball milling, lyophilized and reconstituted with water for injection prior experiment. Different dilutions of nanocrystal dispersion in LAL reagent water were prepared as well as positive and negative control. Despite difficulties to detect gel clots, they were visible in the sample at dilutions 1:75 and below. According to the protocol, the endotoxin limit was estimated to be 25.00 EU/ml, which corresponds to <12.50 EU/mg of DK-I-56-1. This value relates to the endotoxin limit for diazepam, with the similar dosing regimen as proposed for DK-I-56-1.", journal = "NANOGVA Symposium, October 5th - 6th, 2023, Geneva, Switzerland", title = "Estimation of endotoxin level in nanocrystal dispersion of DK-I-56-1 intended for parenteral administration", url = "https://hdl.handle.net/21.15107/rcub_farfar_5090" }
Mitrović, J., Ilić, T., Jančić, I., Bufan, B., Savić, M.,& Savić, S.. (2023). Estimation of endotoxin level in nanocrystal dispersion of DK-I-56-1 intended for parenteral administration. in NANOGVA Symposium, October 5th - 6th, 2023, Geneva, Switzerland. https://hdl.handle.net/21.15107/rcub_farfar_5090
Mitrović J, Ilić T, Jančić I, Bufan B, Savić M, Savić S. Estimation of endotoxin level in nanocrystal dispersion of DK-I-56-1 intended for parenteral administration. in NANOGVA Symposium, October 5th - 6th, 2023, Geneva, Switzerland. 2023;. https://hdl.handle.net/21.15107/rcub_farfar_5090 .
Mitrović, Jelena, Ilić, Tanja, Jančić, Ivan, Bufan, Biljana, Savić, Miroslav, Savić, Snežana, "Estimation of endotoxin level in nanocrystal dispersion of DK-I-56-1 intended for parenteral administration" in NANOGVA Symposium, October 5th - 6th, 2023, Geneva, Switzerland (2023), https://hdl.handle.net/21.15107/rcub_farfar_5090 .