Drug Delivery Strategies for Enhancing the Therapeutic Efficacy of Toxin-Derived Anti-Diabetic Peptides

• Published in: Toxins 2020-05, Vol.12 (5), p.313
• Main Authors: Amatya, Reeju, Park, Taehoon, Hwang, Seungmi, Yang, JaeWook, Lee, Yoonjin, Cheong, Heesun, Moon, Cheol, Kwak, Hyun Duck, Min, Kyoung Ah, Shin, Meong Cheol
• Format: Article
• Language: English
• Subjects: Amino acids; Amphibian Venoms - chemistry; Amphibian Venoms - pharmacokinetics; Amphibian Venoms - therapeutic use; Amphibians; Animal models; Animals; anti-diabetic peptide; Antidiabetics; Antimicrobial agents; Biomarkers - blood; Blood circulation; Blood Glucose - drug effects; Blood Glucose - metabolism; cell-penetrating peptide; Cytotoxicity; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Drug Carriers; Drug Compounding; Drug delivery; Drug Delivery Systems; Drug development; Exenatide - chemistry; Exenatide - pharmacokinetics; Exenatide - therapeutic use; Glucose; Half-Life; Humans; Hypoglycemic Agents - chemistry; Hypoglycemic Agents - pharmacokinetics; Hypoglycemic Agents - therapeutic use; Insulin resistance; Mollusks; Peptides; Plasma; plasma half-life; Review; Secretions; Skin; Therapeutic applications; toxin; Toxins; Toxins, Biological - chemistry; Toxins, Biological - pharmacokinetics; Toxins, Biological - therapeutic use
• ISSN: 2072-6651; 2072-6651
• DOI: 10.3390/toxins12050313

Toxin peptides derived from the skin secretions of amphibians possess unique hypoglycemic activities. Many of these peptides share cationic and amphipathic structural similarities and appear to possess cell-penetrating abilities. The mechanism of their insulinotropic action is yet not elucidated, but they have shown great potential in regulating the blood glucose levels in animal models. Therefore, they have emerged as potential drug candidates as therapeutics for type 2 diabetes. Despite their anti-diabetic activity, there remain pharmaceutical challenges to be addressed for their clinical applications. Here, we present an overview of recent studies related to the toxin-derived anti-diabetic peptides derived from the skin secretions of amphibians. In the latter part, we introduce the bottleneck challenges for their delivery in vivo and general drug delivery strategies that may be applicable to extend their blood circulation time. We focus our research on the strategies that have been successfully applied to improve the plasma half-life of exendin-4, a clinically available toxin-derived anti-diabetic peptide drug.