An ultrafast insulin formulation enabled by high-throughput screening of engineered polymeric excipients

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

Standard

An ultrafast insulin formulation enabled by high-throughput screening of engineered polymeric excipients. / Mann, Joseph L.; Maikawa, Caitlin L.; Smith, Anton A.A.; Grosskopf, Abigail K.; Baker, Sam W.; Roth, Gillie A.; Meis, Catherine M.; Gale, Emily C.; Liong, Celine S.; Correa, Santiago; Chan, Doreen; Stapleton, Lyndsay M.; Yu, Anthony C.; Muir, Ben; Howard, Shaun; Postma, Almar; Appel, Eric A.

In: Science Translational Medicine, Vol. 12, No. 550, eaba6676, 07.2020.

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

Harvard

Mann, JL, Maikawa, CL, Smith, AAA, Grosskopf, AK, Baker, SW, Roth, GA, Meis, CM, Gale, EC, Liong, CS, Correa, S, Chan, D, Stapleton, LM, Yu, AC, Muir, B, Howard, S, Postma, A & Appel, EA 2020, 'An ultrafast insulin formulation enabled by high-throughput screening of engineered polymeric excipients', Science Translational Medicine, vol. 12, no. 550, eaba6676. https://doi.org/10.1126/scitranslmed.aba6676

APA

Mann, J. L., Maikawa, C. L., Smith, A. A. A., Grosskopf, A. K., Baker, S. W., Roth, G. A., Meis, C. M., Gale, E. C., Liong, C. S., Correa, S., Chan, D., Stapleton, L. M., Yu, A. C., Muir, B., Howard, S., Postma, A., & Appel, E. A. (2020). An ultrafast insulin formulation enabled by high-throughput screening of engineered polymeric excipients. Science Translational Medicine, 12(550), [eaba6676]. https://doi.org/10.1126/scitranslmed.aba6676

CBE

Mann JL, Maikawa CL, Smith AAA, Grosskopf AK, Baker SW, Roth GA, Meis CM, Gale EC, Liong CS, Correa S, Chan D, Stapleton LM, Yu AC, Muir B, Howard S, Postma A, Appel EA. 2020. An ultrafast insulin formulation enabled by high-throughput screening of engineered polymeric excipients. Science Translational Medicine. 12(550):Article eaba6676. https://doi.org/10.1126/scitranslmed.aba6676

MLA

Vancouver

Mann JL, Maikawa CL, Smith AAA, Grosskopf AK, Baker SW, Roth GA et al. An ultrafast insulin formulation enabled by high-throughput screening of engineered polymeric excipients. Science Translational Medicine. 2020 Jul;12(550). eaba6676. https://doi.org/10.1126/scitranslmed.aba6676

Author

Mann, Joseph L. ; Maikawa, Caitlin L. ; Smith, Anton A.A. ; Grosskopf, Abigail K. ; Baker, Sam W. ; Roth, Gillie A. ; Meis, Catherine M. ; Gale, Emily C. ; Liong, Celine S. ; Correa, Santiago ; Chan, Doreen ; Stapleton, Lyndsay M. ; Yu, Anthony C. ; Muir, Ben ; Howard, Shaun ; Postma, Almar ; Appel, Eric A. / An ultrafast insulin formulation enabled by high-throughput screening of engineered polymeric excipients. In: Science Translational Medicine. 2020 ; Vol. 12, No. 550.

Bibtex

@article{424c4bb4db844ba0ac0b5d263262c6cd,
title = "An ultrafast insulin formulation enabled by high-throughput screening of engineered polymeric excipients",
abstract = "Insulin has been used to treat diabetes for almost 100 years; yet, current rapid-acting insulin formulations do not have sufficiently fast pharmacokinetics to maintain tight glycemic control at mealtimes. Dissociation of the insulin hexamer, the primary association state of insulin in rapid-acting formulations, is the rate-limiting step that leads to delayed onset and extended duration of action. A formulation of insulin monomers would more closely mimic endogenous postprandial insulin secretion, but monomeric insulin is unstable in solution using present formulation strategies and rapidly aggregates into amyloid fibrils. Here, we implement high-throughput-controlled radical polymerization techniques to generate a large library of acrylamide carrier/dopant copolymer (AC/DC) excipients designed to reduce insulin aggregation. Our top-performing AC/DC excipient candidate enabled the development of an ultrafast-absorbing insulin lispro (UFAL) formulation, which remains stable under stressed aging conditions for 25 ± 1 hours compared to 5 ± 2 hours for commercial fast-acting insulin lispro formulations (Humalog). In a porcine model of insulin-deficient diabetes, UFAL exhibited peak action at 9 ± 4 min, whereas commercial Humalog exhibited peak action at 25 ± 10 min. These ultrafast kinetics make UFAL a promising candidate for improving glucose control and reducing burden for patients with diabetes.",
author = "Mann, {Joseph L.} and Maikawa, {Caitlin L.} and Smith, {Anton A.A.} and Grosskopf, {Abigail K.} and Baker, {Sam W.} and Roth, {Gillie A.} and Meis, {Catherine M.} and Gale, {Emily C.} and Liong, {Celine S.} and Santiago Correa and Doreen Chan and Stapleton, {Lyndsay M.} and Yu, {Anthony C.} and Ben Muir and Shaun Howard and Almar Postma and Appel, {Eric A.}",
year = "2020",
month = jul,
doi = "10.1126/scitranslmed.aba6676",
language = "English",
volume = "12",
journal = "Science Translational Medicine",
issn = "1946-6234",
publisher = "american association for the advancement of science",
number = "550",

}

RIS

TY - JOUR

T1 - An ultrafast insulin formulation enabled by high-throughput screening of engineered polymeric excipients

AU - Mann, Joseph L.

AU - Maikawa, Caitlin L.

AU - Smith, Anton A.A.

AU - Grosskopf, Abigail K.

AU - Baker, Sam W.

AU - Roth, Gillie A.

AU - Meis, Catherine M.

AU - Gale, Emily C.

AU - Liong, Celine S.

AU - Correa, Santiago

AU - Chan, Doreen

AU - Stapleton, Lyndsay M.

AU - Yu, Anthony C.

AU - Muir, Ben

AU - Howard, Shaun

AU - Postma, Almar

AU - Appel, Eric A.

PY - 2020/7

Y1 - 2020/7

N2 - Insulin has been used to treat diabetes for almost 100 years; yet, current rapid-acting insulin formulations do not have sufficiently fast pharmacokinetics to maintain tight glycemic control at mealtimes. Dissociation of the insulin hexamer, the primary association state of insulin in rapid-acting formulations, is the rate-limiting step that leads to delayed onset and extended duration of action. A formulation of insulin monomers would more closely mimic endogenous postprandial insulin secretion, but monomeric insulin is unstable in solution using present formulation strategies and rapidly aggregates into amyloid fibrils. Here, we implement high-throughput-controlled radical polymerization techniques to generate a large library of acrylamide carrier/dopant copolymer (AC/DC) excipients designed to reduce insulin aggregation. Our top-performing AC/DC excipient candidate enabled the development of an ultrafast-absorbing insulin lispro (UFAL) formulation, which remains stable under stressed aging conditions for 25 ± 1 hours compared to 5 ± 2 hours for commercial fast-acting insulin lispro formulations (Humalog). In a porcine model of insulin-deficient diabetes, UFAL exhibited peak action at 9 ± 4 min, whereas commercial Humalog exhibited peak action at 25 ± 10 min. These ultrafast kinetics make UFAL a promising candidate for improving glucose control and reducing burden for patients with diabetes.

AB - Insulin has been used to treat diabetes for almost 100 years; yet, current rapid-acting insulin formulations do not have sufficiently fast pharmacokinetics to maintain tight glycemic control at mealtimes. Dissociation of the insulin hexamer, the primary association state of insulin in rapid-acting formulations, is the rate-limiting step that leads to delayed onset and extended duration of action. A formulation of insulin monomers would more closely mimic endogenous postprandial insulin secretion, but monomeric insulin is unstable in solution using present formulation strategies and rapidly aggregates into amyloid fibrils. Here, we implement high-throughput-controlled radical polymerization techniques to generate a large library of acrylamide carrier/dopant copolymer (AC/DC) excipients designed to reduce insulin aggregation. Our top-performing AC/DC excipient candidate enabled the development of an ultrafast-absorbing insulin lispro (UFAL) formulation, which remains stable under stressed aging conditions for 25 ± 1 hours compared to 5 ± 2 hours for commercial fast-acting insulin lispro formulations (Humalog). In a porcine model of insulin-deficient diabetes, UFAL exhibited peak action at 9 ± 4 min, whereas commercial Humalog exhibited peak action at 25 ± 10 min. These ultrafast kinetics make UFAL a promising candidate for improving glucose control and reducing burden for patients with diabetes.

UR - http://www.scopus.com/inward/record.url?scp=85087474665&partnerID=8YFLogxK

U2 - 10.1126/scitranslmed.aba6676

DO - 10.1126/scitranslmed.aba6676

M3 - Journal article

C2 - 32611683

AN - SCOPUS:85087474665

VL - 12

JO - Science Translational Medicine

JF - Science Translational Medicine

SN - 1946-6234

IS - 550

M1 - eaba6676

ER -