All Publications


  • Full closed loop open-source algorithm performance comparison in pigs with diabetes. Clinical and translational medicine Lal, R. A., Maikawa, C. L., Lewis, D., Baker, S. W., Smith, A. A., Roth, G. A., Gale, E. C., Stapleton, L. M., Mann, J. L., Yu, A. C., Correa, S., Grosskopf, A. K., Liong, C. S., Meis, C. M., Chan, D., Garner, J. P., Maahs, D. M., Buckingham, B. A., Appel, E. A. 2021; 11 (4): e387

    Abstract

    Understanding how automated insulin delivery (AID) algorithm features impact glucose control under full closed loop delivery represents a critical step toward reducing patient burden by eliminating the need for carbohydrate entries at mealtimes. Here, we use a pig model of diabetes to compare AndroidAPS and Loop open-source AID systems without meal announcements. Overall time-in-range (70-180mg/dl) for AndroidAPS was 58% ± 5%, while time-in-range for Loop was 35% ± 5%. The effect of the algorithms on time-in-range differed between meals and overnight. During the overnight monitoring period, pigs had an average time-in-range of 90% ± 7% when on AndroidAPS compared to 22% ± 8% on Loop. Time-in-hypoglycemia also differed significantly during the lunch meal, whereby pigs running AndroidAPS spent an average of 1.4% (+0.4/-0.8)% in hypoglycemia compared to 10% (+3/-6)% for those using Loop. As algorithm design for closed loop systems continues to develop, the strategies employed in the OpenAPS algorithm (known as oref1) as implemented in AndroidAPS for unannounced meals may result in a better overall control for full closed loop systems.

    View details for DOI 10.1002/ctm2.387

    View details for PubMedID 33931977

  • Enhanced Humoral Immune Response by High Density TLR Agonist Presentation on Hyperbranched Polymers ADVANCED THERAPEUTICS Liong, C. S., Smith, A. A., Mann, J. L., Roth, G. A., Gale, E. C., Maikawa, C. L., Ou, B. S., Appel, E. A. 2021
  • An ultrafast insulin formulation enabled by high-throughput screening of engineered polymeric excipients. Science translational medicine Mann, J. L., Maikawa, C. L., Smith, 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; 12 (550)

    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.

    View details for DOI 10.1126/scitranslmed.aba6676

    View details for PubMedID 32611683

  • A co-formulation of supramolecularly stabilized insulin and pramlintide enhances mealtime glucagon suppression in diabetic pigs. Nature biomedical engineering Maikawa, C. L., Smith, A. A., Zou, L. n., Roth, G. A., Gale, E. C., Stapleton, L. M., Baker, S. W., Mann, J. L., Yu, A. C., Correa, S. n., Grosskopf, A. K., Liong, C. S., Meis, C. M., Chan, D. n., Troxell, M. n., Maahs, D. M., Buckingham, B. A., Webber, M. J., Appel, E. A. 2020

    Abstract

    Treatment of patients with diabetes with insulin and pramlintide (an amylin analogue) is more effective than treatment with insulin only. However, because mixtures of insulin and pramlintide are unstable and have to be injected separately, amylin analogues are only used by 1.5% of people with diabetes needing rapid-acting insulin. Here, we show that the supramolecular modification of insulin and pramlintide with cucurbit[7]uril-conjugated polyethylene glycol improves the pharmacokinetics of the dual-hormone therapy and enhances postprandial glucagon suppression in diabetic pigs. The co-formulation is stable for over 100 h at 37 °C under continuous agitation, whereas commercial formulations of insulin analogues aggregate after 10 h under similar conditions. In diabetic rats, the administration of the stabilized co-formulation increased the area-of-overlap ratio of the pharmacokinetic curves of pramlintide and insulin from 0.4 ± 0.2 to 0.7 ± 0.1 (mean ± s.d.) for the separate administration of the hormones. The co-administration of supramolecularly stabilized insulin and pramlintide better mimics the endogenous kinetics of co-secreted insulin and amylin, and holds promise as a dual-hormone replacement therapy.

    View details for DOI 10.1038/s41551-020-0555-4

    View details for PubMedID 32393892

  • On the Working Mechanisms of Solid-State Double-Layer-Dielectric-Based Organic Field-Effect Transistors and Their Implication for Sensors ADVANCED ELECTRONIC MATERIALS Pfattner, R., Foudeh, A. M., Liong, C., Bettinson, L., Hinckley, A. C., Kong, D., Bao, Z. 2018; 4 (1)