Replacing Pumps with Light Controlled Insulin Delivery
- 37 Downloads
Purpose of Review
The aim of this review is to summarize the development of the photoactivated depot (PAD) approach for the minimally invasive and continuously variable delivery of insulin.
Using an insulin PAD, we have demonstrated that we can release native, bioactive insulin into diabetic animals in response to light signals from a small external LED light source. We have further shown that this released insulin retains bioactivity and reduces blood glucose. In addition, we have designed and constructed second generation materials that have high insulin densities, with the potential for multiple day delivery.
The PAD approach for insulin therapy holds promise for addressing the pressing need for continuously variable delivery methods that do not rely on pumps, and their myriad associated problems.
KeywordsInsulin Protein delivery Light Glucagon Depot Insulin pump Artificial pancreas
The work reviewed in this article was largely executed by a group of talented and dedicated graduate students. They are: Piyush K. Jain, Dipu Karunakaran, Bhagyesh R. Sarode, Karthik Nadendla, Swetha Chintala, Parth Shah and Mayank Sharma.
In addition all animal studies were performed in collaboration with Professor Karen Kover (Childrens’ Mercy Hospital, Kansas City).
The work was funded by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Number DP3DK106921 as well as the support of a University of Missouri Fast Track Award and the UMKC School of Pharmacy Dean’s Bridge Fund.
Compliance with Ethical Standards
Conflict of Interest
Simon H. Friedman has a patent issued (US 10159735), and a patent pending (on Drug Conjugates with Photocleavable Solubility Modulators).
Human and Animal Rights and Informed Consent
All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 8.Forlenza GP, Buckingham B, Maahs DM. Progress in diabetes technology: developments in insulin pumps, continuous glucose monitors, and Progress towards the artificial pancreas. J Pediatr. 2015.Google Scholar
- 19.Heinemann L, Fleming GA, Petrie JR, Holl RW, Bergenstal RM, Peters AL. Insulin pump risks and benefits: a clinical appraisal of pump safety standards, adverse event reporting and research needs. A joint statement of the European Association for the Study of diabetes and the American Diabetes Association diabetes technology working group. Diabetologia. 2015;58(5):862–70.CrossRefGoogle Scholar
- 23.Massa G, Gys I, Eyndt AO, Wauben K, Vanoppen A. Needle detachment from the sure-T¬Æ infusion set in two young children with diabetes mellitus (DM) treated with continuous subcutaneous insulin infusion (CSII) and unexplained hyperglycaemia. J Pediatr Endocrinol Metab. 2015;28(1–2):237–9.PubMedGoogle Scholar
- 24.Moser C, Maurer K, Binder E, Meraner D, Steichen E, Abt D, et al. Needle detachment in a slim and physically active child with insulin pump treatment. Pediatr Diabetes. 2015.Google Scholar
- 25.Plager P, Murati MA, Moran A, Sunni M. Two case reports of retained steel insulin pump infusion set needles. Pediatr Diabetes. 2015.Google Scholar
- 26••.Jain PK, Karunakaran D, Friedman SH. Construction of a photoactivated insulin depot. Angew Chem Int Ed. 2013;52(5):1404–9. This was the first demonstration of the synthesis of insulin PAD materials, and showed that native insulin could be covalently linked to an insoluble resin, and then released in a controlled manner using light from an LED. CrossRefGoogle Scholar
- 27••.Sarode BR, Kover K, Tong PY, Zhang C, Friedman SH. Light control of insulin release and blood glucose using an injectable photoactivated depot. Mol Pharm. 2016;13(11):3835–41. This was the first in-vivo demonstration of the insulin PAD approach. It demonstrated in diabetic rats that sufficient light could cross the skin during transdermal irradiation to stimulate insulin release. It further showed that insulin was released into the blood rapidly (within five minutes) and maintained its bioactivity, effecting blood glucose reduction.CrossRefGoogle Scholar
- 30.Nadendla K, Sarode BR, Friedman SH. Hydrophobic Tags for Highly Efficient Light-Activated Protein Release. Mol Pharm. 2019.Google Scholar
- 32.Haidar A, Legault L, Messier V, Miter TM, Leroux C, Rabasa-Lhoret R. Comparison of dual-hormone artificial pancreas, single-hormone artificial pancreas, and conventional insulin pump therapy for glycaemic control in patients with type 1 diabetes: An open-label randomized controlled crossover trial. The Lancet Diabetes Endocrinol. 2015;3(2):17–26.CrossRefGoogle Scholar