2025 - Sustainable Industrial Processing Summit
SIPS2025 Volume 7. Tanner Intl. Symp. / Pharmaceutical Sciences and Biotechnology
| Editors: | F. Kongoli, S. Buchmann, M. Bultmann, I. Karim, G. Kimura, G. Knipp, H. Leuenberger, M. Makanga, N. Menshutina, P. Swaan, H. Tarabishi |
| Publisher: | Flogen Star OUTREACH |
| Publication Year: | 2025 |
| Pages: | 177 pages |
| ISBN: | 978-1-998384-50-1 (CD) |
| ISSN: | 2291-1227 (Metals and Materials Processing in a Clean Environment Series) |
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INFLUENCE OF A THERAPEUTIC MONOCLONAL ANTIBODY FORMULATION BEFORE AND AFTER IRRADIATION ON THE SURFACE TENSIOMETRY PROPERTIES OF BLOOD DROPLETS BY THE CONTACT ANGLE METHOD
Davide Rossi1; Giorgia Miolo2;1DEVELOPMENT COOPERATION ASSOCIATION BAZH.I, Maserada Sul Piave, Italy; 2UNIVERSITY OF PADOVA, Padova, Italy;
Type of Paper: Regular
Id Paper: 249
Topic: 73
Abstract:
During storage, transport, dilution and intravenous (i.v.) administration, mAbs are exposed to different stressors, including artificial and indoor ambient light, which can compromise their efficacy and safety. Light can induce concentration-dependent aggregation, leading to a measurable reduction in the drug's ability to bind its target The surface tensiometry properties of monoclonal antibodies (mAbs) were recently characterized using the Solid-like Methodology (SLM) [1] applying the Contact Angle Method (CA) [2]. The SLM consists in the deposition of a hydrophobic, lipophobic and self-repellent “liquid film”, called polyperfluorometylisopropyl ether (PFPE) [3] used as “solid substrate” for the characterization of liquid systems droplets [4]. This SLM consents the determination of Surface Tension (ST; mN/m), Dispersion Component (DC; mN/m) and Polar Component (PC; mN/m) of liquids without the influence of friction forces and surface roughness and was largely applied in the field of pharmaceutical technology [5]. The Well methodology (WM) [5] derives from the concept of Solid-like Methodology (SLM); unlike the SLM, the WM consists in the deposition of an amount of PFPE (PFPEw) leaved in a ceramic concave support (well). When a drop of liquid comes in contact with the surface of the PFPEw, a characteristic meniscus is formed caused by the hydrophilic/lipophilic ratio of the liquid (corresponds to its surface chemistry) in relation to the hydrophobic, lipophobic and self-repellent properties of PFPEw at the interface. The WM was here used to determine the surface tensiometry properties of human blood (Hb, G.M. droplets) and its variations after the addition with Nivolumab/Opdivo® (Opdivo samples/Hb complex system) as such and diluted in glucose and NaCl before and after light treatment with 720.0 and 10.460 KJ/m2. The surface tensiometry parameter used here is the Vertical Drop Speed (VDS: dSA/dt) which measures the rate at which a drop of mAb sample spreads vertically at the interface with PFPEw. As first result, the VDS Opdivoâ formulation values (6.3E-05±4.8E-05) tend to decrease strongly after treatment with 720.0 KJ/m2 (2.9E-05±7.9E-06) and more at 10460 KJ/m2 (2.2E-05±8E-06) due to the degradation of Opdivoâ under the light stressor. Differently, the Hb/Opdivoâ complex system VDS values (9.7E-05±5.3E-05) are quite the same after 720.0 KJ/m2 (1.0E-04±4.0E-05) and slightly decrease only after 10460 KJ/m2 (7.3E-05±3.6E-05). This result appears to be correlated with the presence of blood components in the system, which maintains high VDS values due to the strong affinity between mAb and blood components. The presence of 5% glucose (Opdivoâ-glu) as cosolvent reveals the equilibrium between Opdivoâ-glu (3.4E-05±9.1E-06) and blood (9.6E-05±4.6E-05) in the Hb/Opdivoâ-glu complex system (7.5E-05±3.1E-05). The treatment of Opdivoâ-glu with 720.0 KJ/m2 and 10460 KJ/m2 causes, respectively, slight (Opdivoâ-glu; 2.8E-05±5.2E-06, Hb/Opdivoâ-glu; 8.7E-05±3.8E-05, blood; 9.6E-05±4.6E-05) and strong (Opdivoâ-glu; 5.5E-05±1.6E-05, Hb/Opdivoâ-glu; 1.7E-04±8.1E-05, blood; 9.6E-05±4.6E-05) equilibrium decreases due to the great increase of VDS of Hb/Opdivoâ-glu (10460 KJ/m2). This seems due to the increase of aggregates in Opdivoâ-glu after light treatments amplified by the presence of blood components. The presence of 0.9% NaCl demonstrates a disequilibrium between Opdivoâ-NaCl (6.2E-05±2.1E-05) and blood (9.6E-05±4.6E-05) due to lower VDS value of Hb/Opdivoâ-NaCl.(1.4E-05±1.0E-06). That equilibrium is reached after treatment of Opdivoâ-NaCl with 720.0 KJ/m2 (Opdivoâ-NaCl; 4.8E-05±1.4E-05, Hb/Opdivoâ-glu; 7.1E-05±2.7E-05, blood; 9.6E-05±4.6E-05) and marked decreased after treatment with 10460 KJ/m2 (Opdivoâ-NaCl; 4.7E-05±1.2E-05, Hb/Opdivoâ-glu; 1.2E-04±5E-05, blood; 9.6E-05±4.6E-05). However, the increase of Hb/Hb/Opdivoâ-glu as aggregates in NaCl irradiated Opdivo are formed in less amount. With this work we demonstrate the different behaviour of dark and irradiated samples and the difference between undiluted and diluted (NaCl and glucose) Opdivo samples when come in contact with blood. Therefore, we try to mimic the i.v. administration of this drug: when aggregation takes place, mostly under the light exposure and even more in glucose solution, the WM can promptly detect the physical differences among the samples. Our findings indicate that mAbs should be protected from light, especially during prolonged i.v. administration periods, to avoid aggregate formation and potentially reduction of their therapeutic activity.