Effects of Formulation Variables on the Formation of Nanoparticles Prepared from L-Lactide-Depsipeptide Copolymer

A depsipeptide-lactide copolymer, poly[LA-(Glc-Leu)], was obtained by ring opening copolymerization of L-lactide with a cyclodepsipeptide, cyclo(Glc-Leu). Poly[LA-(Glc-Leu)] nanoparticles were prepared by the oil-in-water solvent evaporation method using Diclofenac Sodium as model hydrophilic drug. In order to both reaching submicron size as well as increasing the grade of monodispersity compared to previous preparation techniques, a microfluidizer as probe ultrasonication device was used. The ultrasonication procedure has been optimized with regard to particle size and monodispersity by changing the different formulation parameters during the preparation step. The drug loading has been improved by varying the concentration of the drug in organic phase. The diclofenac encapsulation efficiency decreased with higher drug concentration in the inner organic phase. The release profile of optimized batch was characterized by a initial burst effect followed by extended release. To estimate main-chain cleavage behavior of optimized polymeric nanoparticles in vivo, the hydrolysis of the particles in vitro was carried out in phosphate buffer with or without Protinease K.