Title:Cell-Penetrating Peptides as a Potential Drug Delivery System for Effective Treatment of Diabetes
Volume: 27
Issue: 6
Author(s): Mallikarjuna Korivi, Yue-Wern Huang and Betty R. Liu*
Affiliation:
- Department of Laboratory Medicine and Biotechnology, College of Medicine, Tzu Chi University, Hualien 97004,Taiwan
Keywords:
Cell-penetrating peptides (CPPs), diabetes, drug delivery system (DDS), hyperglycemia, metabolic syndrome (MetS), type 2 diabetes
(T2D).
Abstract:
Background/Purpose: Type 2 diabetes (T2D) is characterized by hyperglycemia resulting from the
body’s inability to produce and/or use insulin. Patients with T2D often have hyperinsulinemia, dyslipidemia, inflammation,
and oxidative stress, which then lead to hypertension, chronic kidney disease, cardiovascular disease,
and increased risk of morbidity and mortality (9th leading cause globally). Insulin and related pharmacological
therapies are widely used to manage T2D, despite their limitations. Efficient drug delivery systems (DDS)
that control drug kinetics may decrease side effects, allow for efficient targeting, and increase the bioavailability
of drugs to achieve maximum therapeutic benefits. Thus, the development of effective DDS is crucial to beat
diabetes.
Methods: Here, we introduced a highly bioavailable vector, cell-penetrating peptides (CPPs), as a powerful
DDS to overcome limitations of free drug administration.
Results: CPPs are short peptides that serve as a potent tool for delivering therapeutic agents across cell membranes.
Various cargoes, including proteins, DNA, RNA, liposomes, therapeutic molecules, and nanomaterials,
generally retain their bioactivity upon entering cells. The mechanisms of CPPs/cargoes intracellular entry are
classified into two parts: endocytic pathways and direct membrane translocation. In this article, we focus on the
applications of CPPs/therapeutic agents in the treatment of diabetes. Hypoglycemic drugs with CPPs intervention
can enhance therapeutic effectiveness, and CPP-mediated drug delivery can facilitate the actions of insulin.
Numerous studies indicate that CPPs can effectively deliver insulin, produce synergistic effects with immunosuppressants
for successful pancreatic islet xenotransplantation, prolong pharmacokinetics, and retard diabetic
nephropathy.
Conclusion: We suggest that CPPs can be a new generation of drug delivery systems for effective treatment
and management of diabetes and diabetes-associated complications.
