A Glucose-Responsive Glucagon-Micelle for the Prevention of Hypoglycemia DOI Creative Commons
Daniele Vinciguerra,

P S Rajalakshmi,

Jane Yang

et al.

ACS Central Science, Journal Year: 2024, Volume and Issue: 10(11), P. 2036 - 2047

Published: Oct. 2, 2024

While glucose-responsive insulin delivery systems are in widespread clinical use to treat insufficiency, the on-demand supplementation of glucagon for acute hypoglycemia treatment remains understudied. A self-regulated release material is highly desired mitigate potential risks severe insulin-induced hypoglycemia. Here, we describe a polymeric nanosystem with covalently grafted end-group. Under normoglycemic conditions, phenylboronic acid units polymer chain reversibly bind glucose, triggering self-assembly conjugate into micelles. During hypoglycemia, however, micelle disassembles its original, unimeric state, revealing active conjugate. The formulation showed 5-fold increase activity compared native when tested vitro. Glucagon-loaded micelles injected mice prevented or reversed deep administered prior during an challenge. Glucagon was only observed at below counterregulatory threshold and not normoglycemia moderate vivo chronic toxicity analysis, along μPET/μCT imaging, established biosafety profile this demonstrated no organ accumulation. This proof-of-concept work first step toward development translational, stimuli-responsive platform control glycemia.

Language: Английский

USFDA-approved parenteral peptide formulations and excipients: Industrial perspective DOI
Samarth Kumar, Sachin Nashik Sanap,

Milan Vasoya

et al.

Journal of Drug Delivery Science and Technology, Journal Year: 2024, Volume and Issue: 95, P. 105589 - 105589

Published: March 15, 2024

Language: Английский

Citations

7
Glucagon-based therapy for people with diabetes and obesity: What is the sweet spot? DOI Creative Commons
Emma Rose McGlone, Tricia Tan

Peptides, Journal Year: 2024, Volume and Issue: 176, P. 171219 - 171219

Published: April 13, 2024

People with obesity and type 2 diabetes have a high prevalence of metabolic-associated steatotic liver disease, hyperlipidemia cardiovascular disease. Glucagon increases hepatic glucose production; it also decreases fat accumulation, improves lipidemia energy expenditure. Pharmaceutical strategies to antagonize the glucagon receptor improve glycemic outcomes in people obesity, but they increase steatosis worsen dyslipidemia. Co-agonism glucagon-like peptide-1 (GLP-1) receptors has emerged as promising strategy glycemia obesity. Addition agonism enhances weight loss, reduces ameliorates Prior clinical use, however, further studies are needed investigate safety efficacy GLP-1 co-agonists related conditions, specific concerns regarding higher gastrointestinal side effects, loss muscle mass heart rate. Furthermore, differing ratios glucagon:GLP-1 activity vary their effect; optimum balance is yet be identified.

Language: Английский

Citations

2
Application of lyophilization in pharmaceutical injectable formulations: An industry and regulatory perspective DOI
Samarth Kumar, Sachin Nashik Sanap,

Milan Vasoya

et al.

Journal of Drug Delivery Science and Technology, Journal Year: 2024, Volume and Issue: 100, P. 106089 - 106089

Published: Aug. 23, 2024

Language: Английский

Citations

2
A Glucose-Responsive Glucagon-Micelle for the Prevention of Hypoglycemia DOI Creative Commons
Daniele Vinciguerra,

P S Rajalakshmi,

Jane Yang

et al.

ACS Central Science, Journal Year: 2024, Volume and Issue: 10(11), P. 2036 - 2047

Published: Oct. 2, 2024

While glucose-responsive insulin delivery systems are in widespread clinical use to treat insufficiency, the on-demand supplementation of glucagon for acute hypoglycemia treatment remains understudied. A self-regulated release material is highly desired mitigate potential risks severe insulin-induced hypoglycemia. Here, we describe a polymeric nanosystem with covalently grafted end-group. Under normoglycemic conditions, phenylboronic acid units polymer chain reversibly bind glucose, triggering self-assembly conjugate into micelles. During hypoglycemia, however, micelle disassembles its original, unimeric state, revealing active conjugate. The formulation showed 5-fold increase activity compared native when tested vitro. Glucagon-loaded micelles injected mice prevented or reversed deep administered prior during an challenge. Glucagon was only observed at below counterregulatory threshold and not normoglycemia moderate vivo chronic toxicity analysis, along μPET/μCT imaging, established biosafety profile this demonstrated no organ accumulation. This proof-of-concept work first step toward development translational, stimuli-responsive platform control glycemia.

Language: Английский

Citations

1