Not the Usual Suspects: Alternative Surfactants for Biopharmaceuticals
Therapeutically relevant proteins naturally adsorb to interfaces, causing aggregation which in turn potentially leads to numerous adverse consequences such as loss of activity or unwanted immunogenic reactions. Surfactants are ubiquitously used in biotherapeutics drug development to oppose interfacial stress, yet, the choice of the surfactant is extremely limited: to date, only polysorbates (PS20/80) and poloxamer 188 are used in commercial products. However, both surfactant families suffer from severe degradation and impurities of the raw material, which frequently increases the risk of particle generation, chemical protein degradation, and potential adverse immune reactions. Herein, we assessed a total of 40 suitable alternative surfactant candidates and subsequently performed a selection through a three-gate screening process employing four protein modalities encompassing six different formulations.
The screening is based on short-term agitation-induced aggregation studies coupled to particle analysis and surface tension characterization, followed by long-term quiescence stability studies connected to protein purity measurements and particle analysis. The study concludes by assessing the surfactant’s chemical and enzymatic degradation propensity. The candidates emerging from the screening are de novo α-tocopherol-derivatives named VEDG-2.2 and VEDS, produced ad hoc for this study. They display protein stabilization potential comparable or better than polysorbates together with an increased resistance to chemical and enzymatic degradation, thus representing valuable alternative surfactants for biotherapeutics.
Table S1. Details of all the surfactants investigated in this study.
| Index | Name | Category | Screening drop out stage | PubChem SID | CAS No. | MW (Da) | HLB | CMC (w/v%) |
|---|---|---|---|---|---|---|---|---|
| 1 | PS20 | 3 | N/A | 472407007 | 9005-64-5 | 1228 | 16.7 | 0.007 |
| 2 | PS80 | 3 | N/A | 472385962 | 9005-65-6 | 1310 | 15.0 | 0.002 |
| 3 | PLX188 | 3 | N/A | 472405058 | 9003-11-6 | 8400 | 16.0 | 0.400 |
| 4 | Labrafil M2125 CS (Linoleoy Macrogol-6 glycerides) | 1 | 1 | 135278950 | 61789-25-1 | - | - | - |
| 5 | Labrafil M1944 CS | 1 | 1 | 472217119 | 69071-70-1 | - | - | - |
| 6 | Poly(ethylene glycol) monooleate | 1 | 2 | 441152743 | 9004-96-0 | 860 | 13.6 | 0.006 |
| 7 | Lansurf CDE-G | 1 | 1 | 363902551 | 68603-42-9 | - | - | - |
| 8 | Lansurf CDE | 1 | 1 | 363902551 | 68603-42-9 | - | - | - |
| 9 | Lansurf SMO | 1 | 1 | 363898660 | 1338-43-8 | - | - | - |
| 10 | Lansurf STO85 | 1 | 1 | 363898653 | 9005-70-3 | - | - | - |
| 11 | Lansurf STO | 1 | 2 | 341113964 | 26266-58-0 | 957 | 1.8 | - |
| 12 | Lansurf CAPO | 1 | 1 | 48419813 | 68155-09-9 | - | - | - |
| 13 | Suppocire a pellets | 1 | 1 | 135356513 | 85665-33-4 | - | - | - |
| 14 | Gelucire 44/14 (Lauroyl Macrogol-32 glycerides) | 1 | 1 | 441153334 | 57107-95-6 | - | - | - |
| 15 | Gelucire 48/16 pellets (Polyoxyl32 stereate) | 1 | 2 | 441152744 | 9004-99-3 | 622 | 16 | 0.008 |
| 16 | Tefose 63 (PEG-6 stearate and ethylene glycol palmitostearate and PEG-32 stearate) | 1 | 1 | 441152744 | 91031-31-1 | - | - | - |
| 17 | Labrafil M 2130 CS (Lauroyl Macrogol-6 Glyceride) | 1 | 1 | 441153334 | 57107-95-6 | - | - | - |
| 18 | Tefose 1500 (PEG-6 Stearate(and)PEG-32 Stearate) | 1 | 1 | 441152744 | 9004-99-3 | - | - | - |
| 19 | Gelucire 50/13 Pellets (Stearoyl Macrogol-32 Glyceride) | 1 | 1 | 472404499 | 9011-21-6 | - | - | - |
| 20 | Gelucire 43/01 Pellets | 1 | 1 | 470740159 | 85665-33-4 | - | - | - |
| 21 | TCA Sodium Taurocholate duretgul-M-007 | 1 | 1 | 254774705 | 345909-26-4 | - | - | - |
| 22 | TCA Sodium Taurocholate 90% duretgul-M3-013 | 1 | 1 | 254774705 | 345909-26-4 | - | - | - |
| 23 | TCDCA Taurochenodeoxycholate GOSSEBR1-SSS011 | 1 | 1 | 254774705 | 345909-26-4 | - | - | - |
| 24 | TCA Sodium Taurocholate 90% duretgul-M3-003-006 | 1 | 1 | 254774705 | 345909-26-4 | - | - | - |
| 25 | TCA Sodium Taurocholate | 1 | 1 | 254774705 | 345909-26-4 | - | - | - |
| 26 | GLCA Glycolithocholic acid GOSSEBR1-SSS015A | 1 | 1 | 375925049 | 474-74-8 | - | - | - |
| 27 | TCA Sodium Taurocholate 98% duretgul-M3-01 | 1 | 1 | 254774705 | 345909-26-4 | - | - | - |
| 28 | TDCA Taurodeoxycholic acid M03-bigorf11-003 | 1 | 1 | 363898662 | 516-50-7 | - | - | - |
| 29 | TLCA Taurolithocholic acid M03-bigorf11-002 | 1 | 1 | 363898662 | 516-50-7 | - | - | - |
| 30 | KoolAid Surfactant | 1 | 2 | 434274298 | 2306441-11-0 | - | - | - |
| 31 | Tallowamine polyethoxylated | 1 | 2 | 387021720 | 61791-26-2 | 1500 | 5.0 | 0.013 |
| 32 | Cholic glycine | 1 | 1 | 341125635 | 475-31-0 | - | - | - |
| 33 | Kolliphor ELP | 1 | 2 | 470667819 | 61791-12-6 | 2500 | 13.0 | 0.006 |
| 34 | SPGS 550M | 1 | 3 | 329767804 | 81125-67-9 | 1057 | 10.7 | 0.002 |
| 35 | Brij30 | 1 | 1 | 254787116 | 9002-92-0 | - | - | - |
| 36 | PQS-750 | 1 | 2 | 470636525 | 521313-35-9 | 1588 | 14.0 | 0.020 |
| 37 | PS-750-M (FI-750-M) | 1 | 2 | 434214546 | 2135447-74-2 | 16.4 | 0.050 | |
| 38 | VEDS | 2 | 4 | - | - | 1652 | 13.0 | 0.011 |
| 39 | VEDG-2.2 | 2 | 4 | - | - | 1666 | 12.9 | 0.040 |
| 40 | Brij58S | 2 | 4 | - | - | 1447 | 14.9 | 0.008 |
Download the supporting information here: Not the Usual Suspects: Alternative Surfactants for Biopharmaceuticals – Supporting Information
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Sebastian Brosig, Stefano Cucuzza, Tim Serno, Karoline Bechtold-Peters, Jakob Buecheler, Matej Zivec, Oliver Germershaus, Fabrice Gallou, Not the Usual Suspects: Alternative Surfactants for Biopharmaceuticals, ACS Appl. Mater. Interfaces, 2023
https://doi.org/10.1021/acsami.3c05610
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