Nicole Nihant

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 µm), the total pore volume is close to that of the originally dispersed aqueous drug solution.

Effect of the emulsion stability on the morphology and porosity of semicrystalline poly l-lactide microparticles prepared by w/o/w double emulsion-evaporation

Two semi-crystalline poly l-lactides of very different molecular weights have been used as coating polymers in microencapsulation by the w/o/w double emulsion-evaporation technique. The purpose of this paper is to focus on the effect of crystallinity, i.e. of the chain microstructure, of the coating polylactide on the primary emulsion stability, the encapsulation efficiency and, ultimately, the external and internal morphology and porosity of the final microparticles. Crystallizable chains have clearly a deleterious effect on the encapsulation efficiency of indigocarmine used as a probe and on the internal morphology of microparticles. Moreover, a substantial increase in the molecular weight of poly l-lactide (from 60 to 840 kDa) forces to dilute the polymer solution in order to prevent an exceedingly high viscosity and leads to less stable primary emulsions and more porous solid microspheres. Microparticles of semi-crystalline poly l-lactide have proved to be not suitable for the sustained drug release. These observations are in sharp contrast to the poly d.l-lactide (Mn = 50 kDa), used as the amorphous counterpart, which meets the criteria for an efficient microencapsulation, particularly when the primary emulsion is stabilized by gelation.

Microencapsulation by coacervation of poly(lactide-co-glycolide). IV. Effect of the processing parameters on coacervation and encapsulation

Abstract Attention has been paid to phase separation of poly (lactide-co-glycolide) solutions in CH2Cl2 induced by the addition of a silicone oil in order to promote protein microencapsulation. Since the process is very fast, the system is anytime out of equilibrium. The effect of the main processing parameters on the microencapsulation process has been analyzed and has highlighted that kinetics of the main encapsulation steps has a great effect on the characteristics of the final microspheres. These results have been discussed on the basis of a physico-chemical study of coacervation reported in previous papers of this series.

(D, L) Polylactide microspheres as embolic agent

SummaryOwing 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.

Microencapsulation by coacervation of poly(lactide-co-glycolide): 1. Physicochemical characteristics of the phase separation process

Abstract This paper describes the phase separation of different lactide and glycolide copolyester solutions, induced by the addition of silicone oil in order to promote protein microencapsulation. The phase diagrams of the ternary CH2Cl2-copolyester-silicone oil systems were established in relation to the composition of the copolyester and the viscosity, i.e. the molecular weight, of the silicone oil. The phase-separated systems were characterized in terms of weight, volume, composition and viscosity of the coacervate and supernatant. The effect of the nature of the coating polymer and the molecular weight of the coacervation agent (silicone oil) on the characteristics of the phase-separated system is discussed.