Ultra‐Fast Insulin–Pramlintide Co‐Formulation for Improved Glucose Management in Diabetic Rats

Advanced Science

Peyton C. Chen¹  Eric A. Appel¹  Eric T. Vuong¹  Leslee T. Nguyen¹  Caitlin L. Maikawa¹  Andrea I. d'Aquino²  Joseph L. Mann²  Rayhan A. Lal³  Bruce A. Buckingham⁴  David M. Maahs⁴ 

[1] Department of Bioengineering Stanford University Stanford CA 94305 USA;Department of Materials Science & Engineering Stanford University Stanford CA 94305 USA;Department of Medicine (Endocrinology) Stanford University Stanford CA 94305 USA;Department of Pediatrics (Endocrinology) Stanford University Stanford CA 94305 USA;

关键词: amylin;    diabetes;    drug delivery;    hormones;    insulin;   

DOI  :  10.1002/advs.202101575

来源: DOAJ

【 摘 要 】

Abstract Dual‐hormone replacement therapy with insulin and amylin in patients with type 1 diabetes has the potential to improve glucose management. Unfortunately, currently available formulations require burdensome separate injections at mealtimes and have disparate pharmacokinetics that do not mimic endogenous co‐secretion. Here, amphiphilic acrylamide copolymers are used to create a stable co‐formulation of monomeric insulin and amylin analogues (lispro and pramlintide) with synchronous pharmacokinetics and ultra‐rapid action. The co‐formulation is stable for over 16 h under stressed aging conditions, whereas commercial insulin lispro (Humalog) aggregates in 8 h. The faster pharmacokinetics of monomeric insulin in this co‐formulation result in increased insulin–pramlintide overlap of 75 ± 6% compared to only 47 ± 7% for separate injections. The co‐formulation results in similar delay in gastric emptying compared to pramlintide delivered separately. In a glucose challenge, in rats, the co‐formulation reduces deviation from baseline glucose compared to insulin only, or separate insulin and pramlintide administrations. Further, comparison of interspecies pharmacokinetics of monomeric pramlintide suggests that pharmacokinetics observed for the co‐formulation will be well preserved in future translation to humans. Together these results suggest that the co‐formulation has the potential to improve mealtime glucose management and reduce patient burden in the treatment of diabetes.

【 授权许可】

Unknown