Journal
LANGMUIR
Volume 35, Issue 42, Pages 13543-13552Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.langmuir.9b02317
Keywords
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Funding
- AstraZeneca
- ISIS Neutron Facility, STFC
- EPSRC
- Royal Society [IEC\NSFC\181305]
- Marie Curie Fellowship ITN grant under SNAL (Small Nano-objects for Alteration of Lipid-Bilayers) [608184]
- EPSRC [EP/F062966/1]
- EPSRC [EP/F062966/1] Funding Source: UKRI
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The physical stability of a monoclonal antibody (mAb) solution for injection in a prefilled syringe may in part depend on its behavior at the silicone oil/water interface. Here, the adsorption of a mAb (termed COE-3) and its fragment antigen-binding (Fab) and crystallizable (Fc) at the oil/water interface was measured using neutron reflection. A 1.4 +/- 0.1 mu m hexadecane oil film was formed on a sapphire block by a spin-freeze-thaw process, retaining its integrity upon contact with the protein solutions. Measurements revealed that adsorbed COE-3 and its Fab and Fc fragments retained their globular structure, forming layers that did not penetrate substantially into the oil phase. COE-3 and Fc were found to adsorb flat-on to the interface, with denser 45 and 42 angstrom inner layers, respectively, in contact with the oil and a more diffuse 17-21 angstrom outer layer caused by fragments adsorbing in a tilted manner. In contrast, Fab fragments formed a uniform 60 angstrom monolayer. Monolayers were formed under all conditions studied (10-200 ppm, using three isotopic contrasts), although changes in packing density across the COE-3 and Fc layers were observed. COE-3 had a higher affinity to the interface than either of its constituent fragments, while Fab had a lower interfacial affinity consistent with its higher net surface charge. This study extends the application of high-resolution neutron reflection measurements to the study of protein adsorption at the oil/water interface using an experimental setup mimicking the protein drug product in a siliconized prefilled syringe.
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