With several surfactants to choose from, the biopharma industry is still working to identify the most effective, environmentally friendly alternatives to the surfactant Triton X-100 (TX-100). The EU banned that substance in 2021, citing its endocrine-disruptive effects on aquatic life.
Surfactants play a role in developing stable pharma formulations and can also be used as drug delivery systems with antimicrobial peptides.
“Alternatives to TX-100…need to take into account the concentration of the surfactant needed and its range of viral inactivation,” Caryn L. Heldt, PhD, professor of chemical engineering at Michigan Technological University (MTU), tells GEN. “While some alternatives have been found, there may be better ones that are less expensive and function at a lower concentration.”
“Cost and toxicity are among the key attributes that need to be explored,” she continues. “Any viral inactivation component used will need to demonstrate clearance at the end of the process and, if not completely cleared, it will need to demonstrate biocompatibility and low toxicity.”
Several papers have been published to identify comparable replacements. One of the most recent is from MTU in collaboration with Bristol Myers Squibb.
In it, Heldt and colleagues compared two classes of alternative, commercially available surfactants against the nonionic surfactant TX-100 to understand how the sizes of their hydrophilic heads and lengths of their hydrophobic tails affected surfactants’ abilities to inactivate enveloped viruses. They tested the effectiveness of nonionic glucosides and zwitterionic amine oxides against two herpes viruses—Suid herpesvirus 1 and Human herpesvirus 1—and the retrovirus xenotropic murine leukemia virus (XMuLV).
The alternative surfactants were lauryldimethylamine-N-oxide (LDAO), N,N-dimethyl-1-tetradecanamine-N-oxide (TDAO), 3-Laurylamido-N,N’-dimethylpropyl amine oxide (LAPAO), n-octyl-β-d-glucoside (OG), n-Nonyl-β-D-Glucoside (NG), and methyl-6-O-(N-heptylcarbamoyl)-α-D-glucopyranoside (ANAMEG).
Each of these surfactants performed as well or better than TX-100. Against XMuLV, “surfactants with longer alkyl chains achieved maximum log reduction values at 1x critical micelle concentration (CMC),” they noted. For example, at 1 CRM, TDAO achieved an approximate 3.75-log reduction of XMuLV, and NG and OG achieved about a 3-log reduction. TX-100, in contrast, required two-fold CRM to approach a 3-log reduction.
For herpes viruses, each of the surfactants tested were comparable to TX-100, but “surfactants with bulky headgroups, such as LAPAO, showed lower efficacy against XMuLV,” they found.
The most effective surfactant under all conditions appeared to be NG, which has a long hydrophobic tail. Tail length was directly related to viral inactivation, possibly because longer tails have more interaction with the viral lipid envelopes. The NG surfactant, the scientists concluded, “…could function as an eco-friendly surfactant for virus inactivation in bioprocessing. For NG, virus inactivation was independent of all variables tested.”
Additionally, they found that adding salt improved viral inactivation, possibly because the salt reduced the surfactant’s CMC. Also, when viral inactivation occurs without micelle formation, monomeric surfactants may be effective.
Data shows that with both the Vera and PG-4 cell lines, cell survival was highest when using TDAO and LAPAO surfactants.
Surfactants’ viral inactivation mechanism “is influenced by both the surfactant’s properties and the characteristics of the target virus,” Heldt points out. “We are currently exploring how the size of the surfactant head group and the length of its tail correlate with specific inactivation mechanisms.”
The post More TX-100-Comparable Surfactants Identified appeared first on GEN - Genetic Engineering and Biotechnology News.
Surfactants play a role in developing stable pharma formulations and can also be used as drug delivery systems with antimicrobial peptides.
“Alternatives to TX-100…need to take into account the concentration of the surfactant needed and its range of viral inactivation,” Caryn L. Heldt, PhD, professor of chemical engineering at Michigan Technological University (MTU), tells GEN. “While some alternatives have been found, there may be better ones that are less expensive and function at a lower concentration.”
“Cost and toxicity are among the key attributes that need to be explored,” she continues. “Any viral inactivation component used will need to demonstrate clearance at the end of the process and, if not completely cleared, it will need to demonstrate biocompatibility and low toxicity.”
Several papers have been published to identify comparable replacements. One of the most recent is from MTU in collaboration with Bristol Myers Squibb.
In it, Heldt and colleagues compared two classes of alternative, commercially available surfactants against the nonionic surfactant TX-100 to understand how the sizes of their hydrophilic heads and lengths of their hydrophobic tails affected surfactants’ abilities to inactivate enveloped viruses. They tested the effectiveness of nonionic glucosides and zwitterionic amine oxides against two herpes viruses—Suid herpesvirus 1 and Human herpesvirus 1—and the retrovirus xenotropic murine leukemia virus (XMuLV).
The alternative surfactants were lauryldimethylamine-N-oxide (LDAO), N,N-dimethyl-1-tetradecanamine-N-oxide (TDAO), 3-Laurylamido-N,N’-dimethylpropyl amine oxide (LAPAO), n-octyl-β-d-glucoside (OG), n-Nonyl-β-D-Glucoside (NG), and methyl-6-O-(N-heptylcarbamoyl)-α-D-glucopyranoside (ANAMEG).
Each of these surfactants performed as well or better than TX-100. Against XMuLV, “surfactants with longer alkyl chains achieved maximum log reduction values at 1x critical micelle concentration (CMC),” they noted. For example, at 1 CRM, TDAO achieved an approximate 3.75-log reduction of XMuLV, and NG and OG achieved about a 3-log reduction. TX-100, in contrast, required two-fold CRM to approach a 3-log reduction.
For herpes viruses, each of the surfactants tested were comparable to TX-100, but “surfactants with bulky headgroups, such as LAPAO, showed lower efficacy against XMuLV,” they found.
The most effective surfactant under all conditions appeared to be NG, which has a long hydrophobic tail. Tail length was directly related to viral inactivation, possibly because longer tails have more interaction with the viral lipid envelopes. The NG surfactant, the scientists concluded, “…could function as an eco-friendly surfactant for virus inactivation in bioprocessing. For NG, virus inactivation was independent of all variables tested.”
Additionally, they found that adding salt improved viral inactivation, possibly because the salt reduced the surfactant’s CMC. Also, when viral inactivation occurs without micelle formation, monomeric surfactants may be effective.
Data shows that with both the Vera and PG-4 cell lines, cell survival was highest when using TDAO and LAPAO surfactants.
Surfactants’ viral inactivation mechanism “is influenced by both the surfactant’s properties and the characteristics of the target virus,” Heldt points out. “We are currently exploring how the size of the surfactant head group and the length of its tail correlate with specific inactivation mechanisms.”
The post More TX-100-Comparable Surfactants Identified appeared first on GEN - Genetic Engineering and Biotechnology News.