Process conditions for preparing well-defined nano- and microparticles as delivery systems of alkyl gallates

摘要

Dextran-covered poly(D,L-lactide) (PLA) nano-and microparticles were prepared using an emulsion/solvent evaporation (or diffusion) process for the encapsulation of alkyl gallates (AGs).In the first step,a solution of PLA and AG in ethyl acetate was emulsified to give an aqueous phase containing a hydrophobically modified dextran,which acted as a stabilizer.The second step involved solvent evaporation or diffusion.The emulsification conditions were varied,which allowed for the preparation of nanoand microparticle suspensions covering a wide range of surface-average particle diameters from 0.1 μm (sonication) to 500 μm (stirring with a magnetic bar),with narrow and reproducible size distributions.Continuous microfluidic emulsification in a flow-focusing system led to well-defined microparticles,in the 10-50 μm range.Particles loaded with octyl gallate (OG) and nonyl gallate (NG) were obtained using the three processes,and we showed that the encapsulation efficiency of OG and NG varied significantly depending on the emulsification process.The effect of particle size on the mechanism of in vitro release of encapsulated AGs was investigated.The kinetics of release were controlled either by Fickian diffusion within the solid core or swelling and hydrolytic degradation of the PLA matrix,depending on the pH of the external medium.