Paper Number
EF11 

Session
Emulsions, Foams & Interfacial Rheology

Title
Interfacial viscoelasticity of therapeutic protein solutions

Presentation Date and Time
February 13, 2017 (Monday) 4:00

Track / Room
Track 4 / Sandhill Crane

Authors (Click on name to view author profile)

1. Kannan, Aadithya (Stanford University, Department of Chemical Engineering)
2. Shieh, Ian C. (Genentech, Late Stage Pharmaceutical Development)
3. Leiske, Danielle L. (Genentech, Early Stage Pharmaceutical Development)
4. Lin, Gigi (Stanford University, Department of Chemical Engineering)
5. Fuller, Gerald G. (Stanford University, Department of Chemical Engineering)

Author and Affiliation Lines (in printed abstract book)
Aadithya Kannan¹, Ian C. Shieh², Danielle L. Leiske³, Gigi Lin¹, and Gerald G. Fuller^1
1Department of Chemical Engineering, Stanford University, Stanford, CA; ²Late Stage Pharmaceutical Development, Genentech, San Francisco, CA; ³Early Stage Pharmaceutical Development, Genentech, San Francisco, CA

Speaker / Presenter 
Kannan, Aadithya

Text of Abstract
Monoclonal antibodies (mAbs) are proteins that uniquely identify targets within the body, making them well-suited for therapeutic applications. However, these amphiphilic molecules readily adsorb onto air-solution interfaces where they tend to aggregate, and aggregation can negatively impact the potency and immunogenicity of the therapeutic. We investigated two mAbs from Genentech with a high (mAb1) and low (mAb2) propensity to aggregate at air-solution interfaces. The understanding of the interfacial rheological behavior of the two mAbs is crucial in determining their aggregation tendency. To study this, we performed stress relaxation studies under compressive step strain on an air bubble in solution using a custom-built dilatational rheometer. Bubbles were created, aged, and compressed while the bubble image and pressure were recorded. The dilatational relaxation modulus (the change in stress over the strain) was quantified. These viscoelastic interfaces had a relaxation behavior. The initial value (defined as the initial dilatational modulus) and the equilibrated value (the static dilatational modulus) increased as the interface aged and was larger in magnitude for mAb1 compared to mAb2. Next, to study the influence of surfactants in mAb formulations, polyethylene glycol (PEG) was chosen as a model surfactant. In the mixed PEG/mAb system, mAb1 is known to coadsorb with PEG and form domains at the interface. In contrast, PEG entirely covers the interface when mixed with mAb2. This was reflected in the relaxation behavior of the mixed systems. In conclusion, this study shows that mAb aggregation and competitive co-adsorption can be correlated to single bubble studies.