Abstract
Objective
Monoclonal antibodies are in contact with many different materials throughout their life cycle from production to patient administration. Plastic surfaces are commonly found in single use bags, syringes, perfusion bags and tubing and their hydrophobic nature makes them particularly prone for adsorption of therapeutic proteins. The addition of surfactants in therapeutic formulations aims at minimizing surface and interface adsorption of the active molecules. However, their protection efficacy related to the nature of the plastic material is still poorly investigated.
Methods
We use real-time surface-sensitive techniques and immunosorbent assays, to quantify surfactant and monoclonal antibody adsorption on hydrophobic model surfaces and different plastic polymers to analyse the effect of material surface properties on the level of surfactant protection.
Results
We show that Polysorbate 80 protects monoclonal antibodies significantly better from adsorption on a polystyrene surface than on a hexadecane self-assembled monolayer, used as a model surface with similar hydrophobicity. This enhanced protective effect on polystyrene is observed for different antibodies and also other surfactants, and its extent depends on the surfactant concentration for a given antibody concentration. A comparative adsorption study allows ranking different in-use plastics and highlights the dependence of Polysorbate 80 protection efficacy on the nature of the plastic material.
Conclusion
This study demonstrates that, beyond hydrophobicity, the nature of plastic polymer surfaces affects surfactant adsorption and thereby impacts their protection efficacy in therapeutic antibody formulations.
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Lu RM, Hwang YC, Liu IJ, Lee CC, Tsai HZ, Li HJ, et al. Development of therapeutic antibodies for the treatment of diseases. J Biomed Sci. 2020;27:1–30.
Kaplon H, Muralidharan M, Schneider Z, Reichert JM. Antibodies to watch in 2020. MAbs. Taylor and Francis Inc.; 2020;12:e1703531.
Moussa EM, Panchal JP, Moorthy BS, Blum JS, Joubert MK, Narhi LO, et al. Immunogenicity of therapeutic protein aggregates. J Pharm Sci. 2016;105:417–30.
Khan TA, Mahler H-C, Kishore RSK. Key interactions of surfactants in therapeutic protein formulations: a review. Eur J Pharm Biopharm. 2015;97:60–7.
Gervasi V, Dall Agnol R, Cullen S, McCoy T, Vucen S, Crean A. Parenteral protein formulations: an overview of approved products within the European Union. Eur J Pharm Biopharm. 2018;131:8–24.
Zhang Z, Orski S, Woys AM, Yuan G, Zarraga IE, Wagner NJ, et al. Adsorption of polysorbate 20 and proteins on hydrophobic polystyrene surfaces studied by neutron reflectometry. Colloids Surfaces B Biointerfaces. 2018;168:94–102.
Browne MM, Lubarsky GV, Davidson MR, Bradley RH. Protein adsorption onto polystyrene surfaces studied by XPS and AFM. Surf Sci. 2004;553:155–67.
Kapp SJ, Larsson I, Van De Weert M, Cárdenas M, Jorgensen L. Competitive adsorption of monoclonal antibodies and nonionic surfactants at solid hydrophobic surfaces. J Pharm Sci. 2015;104:593–601.
Couston RG, Skoda MW, Uddin S, Van Der Walle CF. Adsorption behavior of a human monoclonal antibody at hydrophilic and hydrophobic surfaces. MAbs. 2013;5:126–39.
Sacha GA, Saffell-Clemmer W, Abram K, Akers MJ. Practical fundamentals of glass, rubber, and plastic sterile packaging systems. Pharm Dev Technol. 2010;15:6–34.
Le Basle Y, Chennell P, Tokhadze N, Astier A, Sautou V. Physicochemical stability of monoclonal antibodies: a review. J Pharm. 2020;109:169–90.
Lefebvre G, Bruckert F, Filipe V, Huille S, Weidenhaupt M. Adsorption rate constants of therapeutic proteins and surfactants for material surfaces. Colloids Surfaces B Biointerfaces. 2021;203:111722.
Nault L, Guo P, Jain B, Brechet Y, Bruckert F, Weidenhaupt M. Human insulin adsorption kinetics, conformational changes and amyloidal aggregate formation on hydrophobic surfaces. Acta Biomater. 2013;9:5070–9.
Prime KL, Whitesides GM. Self-assembled organic monolayers: model systems for studying adsorption of proteins at surfaces. Science. 1991;252:1164–7.
Dixit N, Maloney KM, Kalonia DS. The effect of tween® 20 on silicone oil–fusion protein interactions. Int J Pharm. 2012;429:158–67.
Joshi O, McGuire J. Adsorption behavior of lysozyme and tween 80 at hydrophilic and hydrophobic silica-water interfaces. Appl Biochem Biotechnol. 2009;152:235–48.
Kim HL, Mcauley A, Livesay B, Gray WD, Mcguire J. Modulation of protein adsorption by Poloxamer 188 in relation to Polysorbates 80 and 20 at solid surfaces. J Pharm Sci . 2014;103:1043–1049.
Kannan A, Shieh IC, Negulescu PG, Chandran Suja V, Fuller GG. Adsorption and aggregation of monoclonal antibodies at silicone oil-water interfaces. Mol Pharm. 2021;18:1656–65.
Zangmeister RA. Application of x-ray photoelectron spectroscopic analysis to protein adsorption on materials relevant to biomanufacturing. J Pharm Sci. 2012;101:1639–44.
Mahler H-C, Huber F, Kishore RSK, Reindl J, Rückert P, Müller R. Adsorption behavior of a surfactant and a monoclonal antibody to sterilizing-grade filters. J Pharm Sci. 2010;99:2620–7.
Vijaya Bhaskar TB, Roch T, Romero O, Ma N, Kratz K, Lendlein A. Single and competitive protein adsorption on polymeric surfaces. Polym Adv Technol. 2015;26:1387–93.
Zheng K, Kapp M, Boccaccini AR. Protein interactions with bioactive glass surfaces: a review. Appl Mater Today. 2019;15:350–71.
Thyparambil AA, Wei Y, Latour RA. Evaluation of the effectiveness of surfactants and denaturants to elute and denature adsorbed protein on different surface chemistries. Langmuir. 2015;31:11814–24.
Grigolato F, Arosio P. The role of surfaces on amyloid formation. Biophys Chem. 2021;270:106533.
ACKNOWLEDGMENTS AND DISCLOSURES
The authors thank Matthieu Weber for excellent technical expertise with XPS acquisition. The authors declare no conflicts of interest.
Funding
GL and RAPJ were supported by an ANRT Cifre PhD grant (2017/0735; 2020/1349). This work was supported by the French National Research Agency in the framework of the “Investissements d’avenir” program (ANR-15-IDEX-02).
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GL developed the methodology and did the experimental work together with AM and RAPJ; VF and SH provided the molecules for the study; VF, SH, FB and MW are responsible for the supervision, the conceptualization, the formal analysis and the validation; GL and MW prepared the manuscript; VF and SH together with FB and MW secured the funding.
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Lefebvre, G., Maze, A., Alvarez-Palencia Jimenez, R. et al. Surfactant Protection Efficacy at Surfaces Varies with the Nature of Hydrophobic Materials. Pharm Res 38, 2157–2166 (2021). https://doi.org/10.1007/s11095-021-03133-6
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DOI: https://doi.org/10.1007/s11095-021-03133-6