Long-acting preparations of exenatide

Figures & data

Table 1 Summary of long-acting exenatide preparations

Preparation method	SR period/Half-life	Advantage(s)	Disadvantage(s)
Microsphere		• Technology is mature • Easy to adjust SR period	• Usually requires subcutaneous injection
PLGA microsphere	5–30 d; mostly 30 d	• PLGA is biocompatible and biodegradable • Approved by FDA
Polysaccharide microsphere	21 d	• Better encapsulation rate than PLGA microspheres	• Relatively elevated inflammation compared with PLGA microspheres
Phase-transition gel in situ	Several days to 360 d	• Use of organic solvent avoided • Easy to prepare	• Severe initial burst in the phase-transition process
Implantable device	21 d	• Avoidance of severe initial burst that is found with phase-transition gel	• Usually surgery is required to implant the device
Structure modification		• Well established and versatile strategy to attain desired properties	• Relatively short SR time • High cost • Safety and efficiency of new molecules need to be evaluated
PEGylation	43 h	• Reduces the immunogenicity	• Yields complex product mixtures • Harmful to kidneys
Introduction of a lysine residue	40 h	• Decreases the degradation by metabolic enzymes	• Lack of detailed data in vivo
Recombinant polypeptide exenatide-XTEN	139 h	• XTEN technology can be universal to peptides and proteins	• Sophisticated
Conjugation with hyaluronate	96 h	• High bio-conjugation efficiency to hyaluronate of 90%	• Slight reduction of insulinotropic activity
Conjugation with acid (lauric, palmitic, lithocholic)	4–20 h		• Slight reduction of cell viability
PLGA microparticles	7 d	• Pulmonary delivery

Notes: For sustained-release (SR) preparations, the SR time is given; for structurally modified molecules, the plasma half-life is given. Data presented are based on the literature cited in this review; the same technologies may result in different data in other research.

Abbreviations: d, days; FDA, US Food and Drug Administration; h, hours; PEG, polyethylene glycol; PLGA, poly(lactic-co-glycolic acid); XTEN, half-life extension technology.

Figure 1 Sequence of exenatide.