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

Abstract

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.

Being Stung Once or Twice by Bees (Apis mellifera L.) Slightly Disturbed the Serum Metabolome of SD Rats to a Similar Extent

“…For example, both melittin and bee venom can significantly reduce the levels of serum glucose and lipids, mainly by depolarizing pancreatic γ cells to increase insulin secretion [ 33 , 34 ]. In the treatment of diabetes, it is very important to increase insulin secretion and lipid regulatory mechanisms to reduce blood sugar levels by developing and utilizing various drugs, including animal and plant toxins [ 35 , 36 , 37 ]. In this study, bee stings significantly reduced serum glucose levels.…”

Venom Peptides, Polyphenols and Alkaloids: Are They the Next Antidiabetics That Will Preserve β-Cell Mass and Function in Type 2 Diabetes?

“…These peptides that can enter into cells include bombesin [ 80 ]; crotamine [ 81 ] members from Pipidae and Ranidae families isolated from the skin of amphibians [ 82 ]; Brevinin-2-related peptide (B2RP), a peptide of the northern frog ( Lithobates septentrionalis ); Alyteserin-2a of the midwife toad ( Alytes obstetricans ); Hymenochirin-1b of the African dwarf frog ( Hymenochirus boettgeri ); Magainin-AM1 and AM2 of xenopus amieti ; and Esculentin-2Cha of the Chiricahua leopard frog ( Lithobates chiricahuensis ). The peptides enter into the cells, depolarize the β-cell membrane and stimulate insulin secretion [ 83 ]. These peptides could pave the way for the development of a new class of antidiabetic drugs, although they may also lead to hypoglycemia.…”

Neuroprotective effect of a novel brain-derived peptide, HIBDAP, against oxygen-glucose deprivation through inhibition of apoptosis in PC12 cells

“…Recently, peptides have been widely concerned because they represent an increasingly popular class of therapeutic agent [3], especially in the eld of diabetes treatment [4] and tumor [5]. Compared to traditional drugs, peptide drugs have several bene cial properties such as less toxicity, accumulation in tissue and drug-drug interactions, and high biological and structural diversity [6].…”