Modulation of protein release from penta-block copolymer microspheres.

Releasing a protein according to a zero-order profile without protein denaturation during the polymeric microparticle degradation process is very challenging. The aim of the current study was to develop protein-loaded microspheres with new PLGA based penta-block copolymers for a linear sustained protein release. Lysozyme was chosen as model protein and 40 µm microspheres were prepared using the solid-in-oil-in-water solvent extraction/evaporation process. Two types of PLGA-P188-PLGA penta-block copolymers were synthetized with two PLGA-segments molecular weight (20 kDa or 40 kDa). The resulting microspheres (50P20-MS and 50P40-MS) had the same size, an encapsulation efficiency around 50-60% but different porosities. Their protein release profiles were complementary: linear but non complete for 50P40-MS, non linear but complete for 50P20-MS. Two strategies, polymer blending and microsphere mixing, were considered to match the release to the desired profile. The (1:1) microsphere mixture was successful. It induced a bi-phasic release with a moderate initial burst (around 13%) followed by a nearly complete linear release for 8 weeks. This study highlighted the potential of this penta-block polymer where the PEO block mass ratio influence clearly the Tg and consequently the microsphere structure and the release behavior at 37 °C. The (1:1) mixture was a starting point but could be finely tuned to control the protein release.

Behavior of poly(d,l-lactic-co-glycolic acid) (PLGA)-based droplets falling into a complex extraction medium simulating the prilling process.

HYPOTHESIS: Prilling process is one of advanced techniques for manufacturing microspheres of controlled and uniform size. In this process, homogenous polymer droplets fall into an extraction medium. The aim of this study was to identify the key parameters influencing the behavior of PLGA polymer-based droplets falling into a complex extraction medium, to select appropriate conditions for prilling. EXPERIMENTS: Polymer solutions and extraction media were characterized by determining their viscosity, density and surface tension. A simple model simulating the prilling process was developed to study droplet behavior. Particle shape and velocity at the air-liquid interface and during sedimentation in the container were analyzed step by step. The correlations between the variables studied were visualized by principal component analysis (PCA). FINDINGS: Droplet deformation at the interface greatly affected the recovery and final particle shape. It depended on the viscosity ratio of polymer solution/extraction medium. The particle shape recovery depended on the viscosity and density of extraction media and polymer solutions. The solidification speed is also an important parameter. In media which the solvent diffused slowly, particles were able to relax and recover their shape, however, they can also deform during sedimentation and collision with the bottom of the cuvette.