Academic Journal
Correlation between protein-polydimethylsiloxane visible particle formation and computationally derived antibody surface properties.
| Τίτλος: | Correlation between protein-polydimethylsiloxane visible particle formation and computationally derived antibody surface properties. |
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| Συγγραφείς: | Hirayama K; Formulation Development Department, Chugai Pharmaceutical Co., Ltd., 5-5-1 Ukima, Kita-ku, Tokyo, Japan. Electronic address: hirayama.kazunori24@chugai-pharm.co.jp., Arai K; Formulation Development Department, Chugai Pharmaceutical Co., Ltd., 5-5-1 Ukima, Kita-ku, Tokyo, Japan., Fukuda M; Formulation Development Department, Chugai Pharmaceutical Co., Ltd., 5-5-1 Ukima, Kita-ku, Tokyo, Japan. Electronic address: fukuda.masakazu43@chugai-pharm.co.jp., Saitoh S; Formulation Development Department, Chugai Pharmaceutical Co., Ltd., 5-5-1 Ukima, Kita-ku, Tokyo, Japan., Hashimoto D; Formulation Development Department, Chugai Pharmaceutical Co., Ltd., 5-5-1 Ukima, Kita-ku, Tokyo, Japan., Aiba Y; Formulation Development Department, Chugai Pharmaceutical Co., Ltd., 5-5-1 Ukima, Kita-ku, Tokyo, Japan. |
| Πηγή: | Journal of pharmaceutical sciences [J Pharm Sci] 2026 Aug; Vol. 115 (8), pp. 104364. Date of Electronic Publication: 2026 Jun 15. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Country of Publication: United States NLM ID: 2985195R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-6017 (Electronic) Linking ISSN: 00223549 NLM ISO Abbreviation: J Pharm Sci Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2016- : New York, NY : Elsevier Original Publication: Easton, Pa., American Pharmaceutical Assn. |
| Ιατρικοί όροι (MeSH): | Antibodies, Monoclonal*/chemistry , Dimethylpolysiloxanes*/chemistry, Poloxamer/chemistry ; Computational Chemistry/methods ; Surface Properties ; Hydrophobic and Hydrophilic Interactions ; Adsorption |
| Περίληψη: | Proteinaceous visible particles (pVPs) form through protein adsorption and aggregation at interfaces. Their formation risk varies widely among biopharmaceutical proteins. We developed a computational chemistry approach to quantitatively compare and predict the risk of protein-polydimethylsiloxane visible particles (psVPs)-a representative pVP type in poloxamer 188 (PX188)-based monoclonal antibody (mAb) formulations-across multiple mAbs by quantifying computationally derived surface charge and hydrophobic patches. First, we established an accelerated assessment system by lowering PX188 concentration, enabling rapid quantification of psVP formation risk for eight mAbs in siliconized polymer pre-filled syringes (PFS). Next, we quantified surface charge and hydrophobic patches on each mAb's molecular surface and assessed their association with psVP risk. Charge patches contributed more to psVP formation than hydrophobic patches in this system. A composite feature combining the total area of charge patches and the combined area of the top five hydrophobic patches showed the highest correlation with psVP formation among the evaluated features. Finally, we quantified the effect of reducing headspace in PFS as a mitigation strategy. These findings could be utilized for sequence and structure‑based prediction of psVP risk, supporting the design of lower‑risk mAbs and early decision‑making on mitigation strategies-such as headspace reduction-during biopharmaceutical development. (Copyright © 2026 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work presented in this study. |
| Contributed Indexing: | Keywords: Charge patch; Computational chemistry; Headspace; Hydrophobic patch; Monoclonal antibodies; Poloxamer 188; Polydimethylsiloxane; Pre-filled syringe; Protein aggregation; Visible particles |
| Substance Nomenclature: | 0 (Antibodies, Monoclonal) 0 (Dimethylpolysiloxanes) 63148-62-9 (baysilon) 106392-12-5 (Poloxamer) |
| Entry Date(s): | Date Created: 20260615 Date Completed: 20260904 Latest Revision: 20260904 |
| Update Code: | 20260905 |
| DOI: | 10.1016/j.xphs.2026.104364 |
| PMID: | 42297290 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1520-6017 |
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| DOI: | 10.1016/j.xphs.2026.104364 |