Aarhus University Seal / Aarhus Universitets segl

The Use of Surfactants to Solubilise a Glucagon Analogue

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Standard

The Use of Surfactants to Solubilise a Glucagon Analogue. / Madsen, Jens Kvist; Giehm, Lise; Otzen, Daniel E.

In: Pharmaceutical Research, Vol. 35, No. 12, 235, 12.2018.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Madsen, JK, Giehm, L & Otzen, DE 2018, 'The Use of Surfactants to Solubilise a Glucagon Analogue', Pharmaceutical Research, vol. 35, no. 12, 235. https://doi.org/10.1007/s11095-018-2494-2

APA

CBE

Madsen JK, Giehm L, Otzen DE. 2018. The Use of Surfactants to Solubilise a Glucagon Analogue. Pharmaceutical Research. 35(12):Article 235. https://doi.org/10.1007/s11095-018-2494-2

MLA

Vancouver

Author

Madsen, Jens Kvist ; Giehm, Lise ; Otzen, Daniel E. / The Use of Surfactants to Solubilise a Glucagon Analogue. In: Pharmaceutical Research. 2018 ; Vol. 35, No. 12.

Bibtex

@article{5069ff19a2194e8e870ba2abebfc4305,
title = "The Use of Surfactants to Solubilise a Glucagon Analogue",
abstract = "PURPOSE: The peptide hormone glucagon, used to treat hypoglycaemic incidents, is prone to aggregation. Generating alternatives with better stability is of pharmaceutical interest in the treatment of diabetes. Here we investigate the impact of six different surfactants on the solubility and stability of ZP-GA-1, a stable version of glucagon.METHODS: We use chemical surfactants (sodium dodecyl sulphate, dodecyl maltoside and polysorbate 20) and the biosurfactants rhamnolipid, sophorolipid and surfactin. We investigate their interaction with ZP-GA-1 by pyrene fluorescence, circular dichroism and isothermal titration calorimetry.RESULTS: All six surfactants induce α-helical structure in ZP-GA-1, SDS having the biggest impact and polysorbate 20 the smallest. SDS keeps ZP-GA-1 solubilised over >48 days as opposed to 29 days in DDM, 3 days in polysorbate 20 and 0 days in buffer. Similarly, much less SDS than DDM, polysorbate 20 or biosurfactant is needed to redissolve aggregated ZP-GA-1. ITC confirms this trend, with SDS exhibiting very strong, and polysorbate 20 very weak interactions.CONCLUSION: Simple surfactant structures promote stronger peptide interactions. ITC shows promise as a general strategy to predict surfactants' solubilising powers. Stronger enthalpic interactions improved the absolute solubility of ZP-GA-1 and their strength correlated to the absolute solubility of the peptides though not to the kinetics of precipitation.",
author = "Madsen, {Jens Kvist} and Lise Giehm and Otzen, {Daniel E}",
year = "2018",
month = dec,
doi = "10.1007/s11095-018-2494-2",
language = "English",
volume = "35",
journal = "Pharmaceutical Research",
issn = "0724-8741",
publisher = "Springer New York LLC",
number = "12",

}

RIS

TY - JOUR

T1 - The Use of Surfactants to Solubilise a Glucagon Analogue

AU - Madsen, Jens Kvist

AU - Giehm, Lise

AU - Otzen, Daniel E

PY - 2018/12

Y1 - 2018/12

N2 - PURPOSE: The peptide hormone glucagon, used to treat hypoglycaemic incidents, is prone to aggregation. Generating alternatives with better stability is of pharmaceutical interest in the treatment of diabetes. Here we investigate the impact of six different surfactants on the solubility and stability of ZP-GA-1, a stable version of glucagon.METHODS: We use chemical surfactants (sodium dodecyl sulphate, dodecyl maltoside and polysorbate 20) and the biosurfactants rhamnolipid, sophorolipid and surfactin. We investigate their interaction with ZP-GA-1 by pyrene fluorescence, circular dichroism and isothermal titration calorimetry.RESULTS: All six surfactants induce α-helical structure in ZP-GA-1, SDS having the biggest impact and polysorbate 20 the smallest. SDS keeps ZP-GA-1 solubilised over >48 days as opposed to 29 days in DDM, 3 days in polysorbate 20 and 0 days in buffer. Similarly, much less SDS than DDM, polysorbate 20 or biosurfactant is needed to redissolve aggregated ZP-GA-1. ITC confirms this trend, with SDS exhibiting very strong, and polysorbate 20 very weak interactions.CONCLUSION: Simple surfactant structures promote stronger peptide interactions. ITC shows promise as a general strategy to predict surfactants' solubilising powers. Stronger enthalpic interactions improved the absolute solubility of ZP-GA-1 and their strength correlated to the absolute solubility of the peptides though not to the kinetics of precipitation.

AB - PURPOSE: The peptide hormone glucagon, used to treat hypoglycaemic incidents, is prone to aggregation. Generating alternatives with better stability is of pharmaceutical interest in the treatment of diabetes. Here we investigate the impact of six different surfactants on the solubility and stability of ZP-GA-1, a stable version of glucagon.METHODS: We use chemical surfactants (sodium dodecyl sulphate, dodecyl maltoside and polysorbate 20) and the biosurfactants rhamnolipid, sophorolipid and surfactin. We investigate their interaction with ZP-GA-1 by pyrene fluorescence, circular dichroism and isothermal titration calorimetry.RESULTS: All six surfactants induce α-helical structure in ZP-GA-1, SDS having the biggest impact and polysorbate 20 the smallest. SDS keeps ZP-GA-1 solubilised over >48 days as opposed to 29 days in DDM, 3 days in polysorbate 20 and 0 days in buffer. Similarly, much less SDS than DDM, polysorbate 20 or biosurfactant is needed to redissolve aggregated ZP-GA-1. ITC confirms this trend, with SDS exhibiting very strong, and polysorbate 20 very weak interactions.CONCLUSION: Simple surfactant structures promote stronger peptide interactions. ITC shows promise as a general strategy to predict surfactants' solubilising powers. Stronger enthalpic interactions improved the absolute solubility of ZP-GA-1 and their strength correlated to the absolute solubility of the peptides though not to the kinetics of precipitation.

U2 - 10.1007/s11095-018-2494-2

DO - 10.1007/s11095-018-2494-2

M3 - Journal article

C2 - 30324334

VL - 35

JO - Pharmaceutical Research

JF - Pharmaceutical Research

SN - 0724-8741

IS - 12

M1 - 235

ER -