Exenatide Microspheres for Monthly Controlled-Release Aided by Magnesium Hydroxide

Area of Science:

• Biomaterials Science
• Pharmaceutical Technology
• Endocrinology

Background:

• Glucagon-like peptide-1 (GLP-1) receptor agonists are crucial for diabetes management, offering self-regulating glycemic control.
• Long-acting formulations enhance patient compliance and therapeutic efficacy.
• Exenatide, a GLP-1 receptor agonist, benefits from controlled-release delivery systems.

Purpose of the Study:

• To extend the injection interval of exenatide from one week to four weeks.
• To develop a novel controlled-release formulation of exenatide using poly(d, l-lactic-co-glycolic acid) (PLGA) microspheres.
• To investigate the role of magnesium hydroxide (Mg(OH)2) in modulating exenatide release.

Main Methods:

• Incorporation of Mg(OH)2 powder into PLGA microspheres containing exenatide.
• Utilizing an extruding-settling process for microsphere preparation to ensure narrow size distribution and high encapsulation efficiency.
• Conducting pharmacokinetic studies in a rhesus monkey model to evaluate drug release profiles.

Main Results:

• The addition of Mg(OH)2 successfully extended the exenatide injection interval to four weeks.
• Mg(OH)2 acted as a diffusion channel creator and a pH-responsive buffer, controlling PLGA degradation.
• Pharmacokinetic studies confirmed a steady blood concentration of exenatide with reduced CMAX and improved dosage form index.

Conclusions:

• The developed Mg(OH)2-loaded PLGA microspheres provide an effective four-week controlled-release formulation for exenatide.
• This formulation enhances exenatide delivery, potentially improving diabetes management and patient adherence.
• The study demonstrates a promising strategy for developing long-acting injectable therapeutics.