Poly(D,L-lactide) nanocapsules prepared by a solvent displacement process:Influence of the composition on physicochemical and structural properties

Nanocapsules (NC)were prepared by interfacial deposition of preformed biode gradable polymer (PLA(50)) after a solvent displacement process. The influe nce of the composition used for the preparation of NC was evaluated in term s of particle size, polydispersity, zeta potential, homogeneity, and struct ural characteristics of the systems. The nature of the oil phase, polymer m olecular weight, type and concentration of different surfactants were inves tigated to optimize the formulation to obtain NC suitable for intravenous a dministration. The influence of the physicochemical properties of the diffe rent oils used in NC preparation on the NC size was evaluated. The interfac ial tension between the oil and water phases seems to have a greater effect on NC size than the oil viscosity. Miglyol 810 and ethyl oleate lead to th e formation of smaller NC, probably because of the reduced interfacial tens ion. The polymer molecular weight plays only a small role in NC surface cha rge in the presence of lecithin, whereas NC surface charge, size, polydispe rsity, and short-term stability were highly influenced by lecithin purity. It appears that the absence of poloxamer 188 leads to smaller polydispersit y, less contamination with nanospheres, and reduced formation of structures other than NC. Furthermore, electron microscopy and density gradient densi ty techniques were used to examine the structure of the particles formed an d their homogeneity. NC formation was evidenced by the bands with intermedi ate density between nanoemulsion and nanospheres; however, other bands of l ow intensity were observed. The presence of liposomes and multilayers in NC preparation was confirmed by electron microscopy. The percentage of carbox yfluorescein entrapped in different NC formulations allowed us to estimate the contamination by liposomes. It has been show that, under our experiment al conditions, an excess of lecithin is an essential prerequisite for a sta ble preparation of PLA NC. (C) 2000 Wiley-Liss, Inc.