Acidic microclimate pH distribution in PLGA microspheres monitored by confocal laser scanning microscopy

Area of Science:

• Biomaterials science
• Drug delivery systems
• Polymer chemistry

Background:

• Poly(lactic-co-glycolic acid) (PLGA) microspheres are widely used for controlled drug release.
• The acidic microenvironment within PLGA microspheres can affect the stability and efficacy of encapsulated bioactive substances.
• Understanding and controlling the microclimate pH (micropH) is essential for optimizing PLGA-based drug delivery systems.

Purpose of the Study:

• To quantitatively monitor the distribution of microclimate pH (micropH) inside PLGA microspheres.
• To investigate the influence of various formulation variables on the micropH kinetics.
• To establish a method for optimizing PLGA microsphere formulations for pH-sensitive drugs.

Main Methods:

• Adapted a ratiometric method using confocal laser scanning microscopy and Lysosensor yellow/blue dextran.
• Examined micropH distribution kinetics over 4 weeks under physiological conditions.
• Evaluated effects of PLGA molecular weight, lactic/glycolic acid ratio, microsphere size, preparation method (oil-in-oil vs. double emulsion), and blending with polyethylene glycol (PEG).

Main Results:

• Accurately sensed micropH in the acidic range (2.8–5.8).
• Lower molecular weight and lactic-rich PLGA formulations exhibited more acidic and variable micropH.
• Larger microspheres of lower MW polymers were more acidic; PEG blending significantly increased micropH (>5).
• Oil-in-oil emulsion preparation resulted in less acidic microspheres compared to double emulsion.

Conclusions:

• The adapted ratiometric method provides accurate micropH sensing within PLGA microspheres.
• Formulation parameters significantly influence the internal microclimate pH of PLGA microspheres.
• Combining this method with existing techniques allows for pH mapping across the 2.8–8.0 range, enabling optimization for pH-sensitive drug delivery.