Recent Advances in Formulations for Long-Acting Delivery of Therapeutic Peptides

Abstract

Recent preclinical and clinical studies have focused on the active area of therapeutic peptides due to their high potency, selectivity, and specificity in treating a broad range of diseases. However, therapeutic peptides suffer from multiple disadvantages, such as limited oral bioavailability, short half-life, rapid clearance from the body, and susceptibility to physiological conditions (e.g., acidic pH and enzymolysis). Therefore, high peptide dosages and dose frequencies are required for effective patient treatment. Recent innovations in pharmaceutical formulations have substantially improved therapeutic peptide administration by providing the following advantages: long-acting delivery, precise dose administration, retention of biological activity, and improvement of patient compliance. This review discusses therapeutic peptides and challenges in their delivery and explores recent peptide delivery formulations, including micro/nanoparticles (based on lipids, polymers, porous silicon, silica, and stimuli-responsive materials), (stimuli-responsive) hydrogels, particle/hydrogel composites, and (natural or synthetic) scaffolds. This review further covers the applications of these formulations for prolonged delivery and sustained release of therapeutic peptides and their impact on peptide bioactivity, loading efficiency, and (in vitro/in vivo) release parameters.

Poly(l-threonine-co-l-threonine Succinate) Thermogels for Sustained Release of Lixisenatide

“…GLP-1 analogs decrease body weight and are clinically used for diet control. 60,61 The sustained release of lixisenatide from the PTTs thermogel significantly reduced the body weight of rats over 7 days compared with that of untreated diabetic rats (Figure 5c). The reduction in body weight due to the GLP-1 receptor agonist is governed by the neural pathways involved in food uptake.…”

Antimicrobial Peptides and Their Assemblies

“…Furthermore, peptide drugs are not limited to AMPs, and reviewing their formulations in general can contribute to our understanding of important requirements for formulating AMPs. A major review recently discussed successful formulations for peptides; therefore, formulations for AMPs could benefit enormously from a better understanding of the general essentials for peptide drugs [144]. As a good example, insulin therapy started in the 1920s, becoming a landmark for the development of more than 60 peptide drugs approved by the FDA [145].…”