Engineering Insulin Cold Chain Resilience to Improve Global Access.
Caitlin L. Maikawa,Joseph L. Mann,Aadithya Kannan,Catherine M. Meis,Abigail K. Grosskopf,Ben S. Ou,Anton A. A. Autzen,Anton A. A. Autzen,Gerald G. Fuller,David M. Maahs,Eric A. Appel +10 more
TLDR
In this paper, the authors developed a simple "drop-in" amphiphilic copolymer excipients to maintain formulation integrity, bioactivity, pharmacokinetics, and pharmacodynamics for over 6 months when subjected to severe stressed aging conditions that cause current commercial formulation to fail in under 2 weeks.About:
This article is published in Biomacromolecules.The article was published on 2021-07-02 and is currently open access. It has received 8 citations till now. The article focuses on the topics: Insulin.read more
Citations
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Affinity-Directed Dynamics of Host-Guest Motifs for Pharmacokinetic Modulation via Supramolecular PEGylation.
Caitlin L. Maikawa,Andrea I. d’Aquino,Eric T. Vuong,Bo Su,Lei Zou,Peyton C. Chen,Leslee T. Nguyen,Anton A. A. Autzen,Anton A. A. Autzen,Joseph L. Mann,Matthew J. Webber,Eric A. Appel +11 more
TL;DR: In this article, the authors show that insulin pharmacokinetics can be modulated by tuning the affinity-directed dynamics of a host-guest motif used to non-covalently endow insulin with a poly(ethylene glycol) (PEG) chain.
Journal ArticleDOI
Stable High-Concentration Monoclonal Antibody Formulations Enabled by an Amphiphilic Copolymer Excipient
John Klich,Catherine M. Kasse,Joseph L. Mann,Yaoqi Huang,Andrea I. d’Aquino,Abigail K. Grosskopf,Julie Baillet,Gerald G. Fuller,Eric A. Appel +8 more
TL;DR: In this paper , an amphiphilic copolymer excipient is proposed to enhance the stability of high-level formulations of clinically relevant monoclonal antibodies without altering their pharmacokinetics or injectability.
Posted ContentDOI
Ultra-fast insulin-pramlintide co-formulation for improved glucose management in diabetic rats
Caitlin L. Maikawa,Peyton C. Chen,Eric T. Vuong,Leslee T. Nguyen,Joseph L. Mann,Andrea I. d’Aquino,Rayhan A. Lal,David M. Maahs,Bruce A. Buckingham,Eric A. Appel +9 more
TL;DR: In this article, a stable co-formulation of monomeric insulin and amylin analogues (lispro and pramlintide) with synchronous pharmacokinetics and ultra-rapid action is presented.
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Single-chain Insulin Analogs Threaded by the Insulin Receptor αCT Domain.
TL;DR: In this paper , the crystal structure of an ultrastable single-chain insulins (SCI) bound to modules of the insulin receptor (IR) ectodomain was determined using diffraction data to a resolution of 2.6 Å.
Posted ContentDOI
Stable High-Concentration Monoclonal Antibody Formulations Enabled by an Amphiphilic Copolymer Excipient
TL;DR: In this paper , an amphiphilic copolymer excipient is proposed to enhance the stability of high-level formulations of clinically relevant monoclonal antibodies without altering their pharmacokinetics or injectability.
References
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Kinetics of insulin aggregation in aqueous solutions upon agitation in the presence of hydrophobic surfaces.
TL;DR: The effects of agitation rate, interfacial interactions, and insulin concentration on the overall aggregation rate were examined, and mathematical modeling of proposed kinetic schemes was employed to identify possible reaction pathways and to explain greater stability at higher insulin concentration.
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Toward understanding insulin fibrillation
Jens Jorgen Veilgaard Brange,Lennart Andersen,Erik D. Laursen,Giorgio Meyn,Eigil Schroder Rasmussen +4 more
TL;DR: In rabbit immunization experiments, insulin fibrils did not elicit an increased immune response with respect to formation of IgG insulin antibodies when compared with native insulin, and the IgE response increased with increasing content of insulin in fibril form.
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Streptozotocin-induced diabetic models in mice and rats.
Kenneth K. Wu,Youming Huan +1 more
TL;DR: This unit describes protocols for the production of insulin deficiency and hyperglycemia in mice and rats, using STZ, which can be employed for assessing the mechanisms of T1DM, screening potential therapies for the treatment of this condition, and evaluation of therapeutic options.
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Excipient-drug interactions in parenteral formulations
TL;DR: This review article will highlight documented interactions, both synergistic and antagonistic, between excipients and drugs in parenteral formulations to gain better understanding and appreciation of the implications of adding formulation ingredients to parenTERal drug products.
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Mechanism of insulin aggregation and stabilization in agitated aqueous solutions
TL;DR: Experimental observations were consistent with the model of monomer denaturation at hydrophobic surfaces followed by the formation of stable intermediate species which facilitated subsequent macroaggregation in insulin aggregation.