Targeting intermolecular interactions to reduce viscosity in monoclonal antibody formulations : a review

Prašnikar, Monika (avtor), Bjelošević Žiberna, Maja (avtor), Ahlin Grabnar, Pegi (avtor)

Monoclonal antibodies (mAb) have transformed modern medicine, offering targeted therapies for cancer, autoimmune disorders, and infectious diseases. To enhance patient convenience, subcutaneous administration is increasingly prioritized, requiring highly concentrated formulations. However, high viscosity of these formulations hinders manufacturability, injectability, and stability. Viscosity-reducing additives are a promising solution, disrupting protein-protein interactions and thereby reducing the viscosity of mAb formulations. Most promising additives are small organic electrolytes, where key properties influencing their efficacy include charge, size, and salt form. Relatively small molecules with three or more charges are most efficient, while the counter-ion provides opportunity for increased solubility and additional interactions. Our data analysis further highlights topological polar surface area and heteroatoms as significant predictors of viscosity reduction, while the role of aromatic moieties remains questionable. Another promising strategy is combining viscosity-reducing additives, which can achieve synergistic viscosity reduction while enhancing stability. Polyelectrolytes also demonstrate promising efficacy via complex formation with mAbs. Conversely, other common excipients of mAb formulations, such as sugars and surfactants, often increase viscosity of the formulation. This review provides a foundation for advancing viscosity-reducing strategies and offers actionable insights to guide future research and development of effective, patient-oriented mAb formulations.

• Jezik: Angleški jezik
• Ključne besede: monoclonal antibody, protein-protein interactions, biopharmaceuticals, highly concentrated mAb formulations, viscosity-reducing additives, subcutaneous administration
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.02 - Pregledni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2025
• Št. strani: Str. 1-14
• Številčenje: Vol. 327, part 2
• PID: 20.500.12556/RUL-175082
• UDK: 616-097
• ISSN pri članku: 0141-8130
• DOI: 10.1016/j.ijbiomac.2025.147515
• COBISS.SI-ID: 248572419
• Datum objave v RUL: 15.10.2025

Gradivo je del revije

• Naslov: International journal of biological macromolecules
• Skrajšan naslov: Int. j. biol. macromol.
• Založnik: Butterworth Scientific Ltd, Elsevier
• ISSN: 0141-8130
• COBISS.SI-ID: 25637888

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: monoklonska protitelesa, interakcije beljakovin-beljakovin, biofarmacevtski izdelki, visoko koncentrirane formulacije monoklonskih protiteles, dodatki za zmanjšanje viskoznosti, subkutana uporaba, farmacevtska kemija

Projekti

• Financer: ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
• Številka projekta: P1-0189
• Naslov: Farmacevtska tehnologija: od dostavnih sistemov učinkovin do terapijskih izidov zdravil pri otrocih in starostnikih

• Financer: ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
• Številka projekta: L1-3160
• Naslov: Razvoj visokokoncentriranih proteinskih formulacij in vrednotenje kinetike absorpcije po subkutani aplikaciji