Microfluidic Regulation of Core-Shell PLGA Microspheres for Sustained Release of Leuprolide Acetate

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Microfluidics Technology

Background:

• Microsphere formulations offer a viable strategy for delivering therapeutic proteins and peptides with short in vivo half-lives.
• These systems protect sensitive biomolecules from degradation, enhancing their therapeutic efficacy.
• Poly(lactic-co-glycolic acid) (PLGA) microspheres are widely explored for controlled drug release applications.

Purpose of the Study:

• To develop poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with leuprolide acetate (LA) utilizing microfluidic technology.
• To investigate the critical parameters influencing LA encapsulation efficiency (EE) and drug loading (DL) in PLGA microspheres.
• To characterize the morphology, particle size, and in vitro release profile of the developed LA-PLGA microspheres.

Main Methods:

• A glass capillary microfluidic device was employed to create water-in-oil-in-water (W/O/W) emulsions.
• Varying concentrations of gelatin (Gel) were incorporated into the internal aqueous phase.
• Different collecting solutions and LA concentrations in the inner phase were systematically evaluated.

Main Results:

• Monodisperse LA-PLGA microspheres with a uniform particle size of approximately 80 μm and a distinct core-shell structure were successfully fabricated.
• A maximum encapsulation efficiency (EE) of 80.28% and drug loading (DL) of 4.24% were achieved at a Gel concentration of 7.5 mg/mL.
• In vitro release studies demonstrated sustained LA release for approximately 28 days, with DL increasing proportionally to the initial LA concentration.

Conclusions:

• Microfluidic technology enables the precise preparation and regulation of LA-PLGA microspheres for sustained drug delivery.
• Gelatin incorporation and collecting solution pH are key factors controlling encapsulation efficiency.
• The developed microfluidic strategy provides a robust platform for formulating water-soluble peptides and proteins into advanced drug delivery systems.