Determination of Diffusion Coefficient of a Small Hydrophobic Probe in Poly(lactide-co-glycolide) Microparticles by Laser Scanning Confocal Microscopy

Abstract

The diffusion coefficient of a small hydrophobic probe in poly(lactide-co-glycolide) (PLGA) microparticles was determined by laser scanning confocal microscopy (LSCM). PLGA microparticles preincubated in a physiological buffer for various times were immersed in an aqueous solution of the pH-insensitive fluorescent probe bodipy at 37 °C. Probe concentration gradients inside individual microparticle matrices were then recorded by LSCM, which were accurately fit by the solution to Fick's second law of diffusion to determine an effective probe diffusion coefficient (D) in the polymer matrix. Values of D varied less than expected from the blank eroding polymer and were in the range (3−10) × 10-12 cm2/s. The apparent polymer-water partition coefficient of the probe was also determined to be roughly 20, indicative of strong partitioning into the polymer phase. The diffusion of bodipy in microparticles varied over 3 orders of magnitude between 22 and 43 °C, indicative of transport control in the polymer phase as ...