Polylactide microparticles prepared by double emulsion/evaporation technique. I. Effect of primary emulsion stability.

The process of microencapsulation of proteins by double emulsion/evaporation in a matrix of polylactide (PLA) can be divided into three successive steps: first, an aqueous solution of the active compound is emulsified into an organic solution of the hydrophobic coating polymer; second, this primary water-in-oil emulsion (w/o) is dispersed in water with formation of a double water-oil-water emulsion (w/o/w); third, the organic solvent is removed with formation of solid microparticles. This paper focuses on the effect of primary emulsion stability on the morphology and properties of polylactide microparticles loaded with bovine serum albumin (BSA) used as model drug. Depending on the stability of the primary emulsion, the internal structure of microparticles can be changed from a multivesicular to a matrix-like structure. Similarly, the average porosity can be controlled in a range from a few tenths of a micron to ca. 20 to 30 microns. This morphology control could find potential applications not only for the controlled drug delivery but also for the production of microporous particles intended for some specific applications, such as cell culture supports and chromatographic matrices. Although, the interplay of several processing parameters (polymer precipitation rate, polymer coprecipitation with interfacial compounds such as protein or surfactant, stirring rate...) may not be disregarded, this study also indicated that a high loading of a hydrophilic drug can only be expected from a stable primary emulsion. When the stability of the primary emulsion is such as to prevent formation of macropores (> 10 microns), the total pore volume is close to that of the originally dispersed aqueous drug solution.

Preparation of poly (D,L) lactide microspheres by emulsion-solvent evaporation, and their clinical applications as a convenient embolic material.

The aim of preoperative embolization is to facilitate surgical removal by reducing tumor volume and vascularity, thereby decreasing blood loss during surgery. In a search for a better embolic material, compared to heterogeneous commercial products, we describe here in detail the preparation of poly (D,L) lactide microspheres by an emulsion-solvent evaporation process. The size distribution of the microparticles and their aggregation state--critical parameters in view of such application--have been investigated. Their effectiveness, as an embolic material, has been evaluated by some preliminary experiments undertaken on humans. The results were assessed on clinical and histological grounds.

(D, L) polylactide microspheres as embolic agent. A preliminary study.

Owing to their shape, accurately calibrated microspheres appear to be very suitable material for distal embolization. Moreover, the biocompatible (D, L) polyactide (PLA) microspheres possess two other valuable advantages: easy adjustment of their biodegradation rate, and incorporation of chemotherapeutic agents during their production. The authors describe the preparation of these (D, L) PLA microspheres and their clinical applications as a preliminary step to arterial chemoembolization.