Sedimentation field flow fractionation operated in the steric hyperlayer mode was used to obtain fractions of defined characteristics from crude samples of poly(D,L-lactic-co-glycolic acid) microspheres which were polydisperse in size. In less than ten minutes, Sedimentation Field Flow Fractionation (SdFFF) separation yielded three analytical fractions of very different size and particle size distribution (PSD) characteristics, as determined by granulometric analyses (Coulter Counter((R)), and image analysis of SEM). A crude sample (average size = 45 mum, 105% size polydispersity index) was separated into fractions of 73 mum, 56 mum, 8 mum average diameters which showed a PSD of 39%, 33%, 30%, respectively. Our results demonstrated that SdFFF used in conjunction with particle size analysis offers a new approach to laboratory scale production of drug vectors of a specified average size and reduced size dispersity. In the future, this could be used to select the most convenient particles for drug loading and release.

Rhodamine B-labelled poly (DL-lactide-co-glycolide) (PLAGA) microspheres of 2 different sizes, 1-5 microns and 5-10 microns, were administered as a single dose (1.44 x 10(9) and 1.83 x 10(8) particles, respectively) into the ileal lumen of adult rats. The content of rhodamine in the mesenteric vein and ileal lumen was analysed periodically from 10 min to 48 h as well as the distribution of microspheres in the intestinal mucosa and various other tissues. The concentration of rhodamine decreased progressively in the intestinal lumen and was negligible after 24 h. The number of microspheres in the mesenteric vein increased rapidly and reached a maximum after 4 h whatever the size of the particles. It then decreased progressively, but more rapidly with microspheres > 5 microns than with microspheres < 5 microns. The absorption efficiency was low for the former batch (about 0.11% of the administered dose) and higher for the latter (about 12.7%). The intraileal administration of free rhodamine B was followed by intense labelling of the epithelial cells and basement membranes in mesenteric lymph nodes, spleen, kidney and liver. PLAGA microspheres mainly crossed the intestinal mucosa at the site of Peyer's patches where microspheres of < 5 microns appeared after 3 h. Microspheres > 5 microns were retained in the ileal lumen. A few small microspheres were occasionally observed in the epithelial cells. Only the smallest particles were recovered in the liver, lymph nodes and spleen while basement membranes were always labelled. It is concluded that PLAGA microspheres could be useful for the oral delivery of antigens if their size is between 1 and 5 microns.

The interfacial behavior of poly(D,L-lactide) and poly(D,L-lactide-co-glycolide) acid monolayers spreading at the air/water interface was studied by using a film balance and by measuring contact angles on LB films. The homopolymer of lactic acid gave a more rigid film, with higher surface pressure than the copolymer which contained glycolic units. On compression, it appeared that orientation of the lactic acid units was probably the cause of a well characterized first-order transition for the polymers with high lactic group contents. A less oriented monolayer was observed when the glycolic content increased. For small areas, the high surface pressure was attributed to the strong interactions occuring between lactic groups with the formation of microdomains. We concluded that the glycolic segments were expulsed from the copolymer monolayers but facilitated the respreading of the copolymer by disrupting interactions between lactic groups. In condensed states, the major contribution to the surface free energy, deduced from contact angle measurements, was nonpolar; a small polar component (due to oxygen atoms) was measured. So, we assumed that the lactic groups and particularly the methyl substituents are oriented toward the air phase. This explains the Lifshitz-Van der Waals component of the surface free energy increasing with the lactic unit content.

In this work, the phase separation of different poly(d,l-lactic acid-co-glycolic acid) batches induced by the addition of silicone oil was studied, for peptide microencapsulation purposes. The phase separation phenomena can be divided in 4 steps according to the amount of incompatible polymer added. But the stabilization of the coacervate droplets and, consequently, the formation of the microspheres, can only be obtained in the third step defined as the stability window. Two experimental parameters influencing the presence, the width and the displacement of the stability window inside ternary diagrams, have been studied: the physicochemical nature of the copolymers and the viscosity of the silicone oil. The results are discussed with respect to the presence of low molecular weight compounds in the studied polymer batches. It is concluded that this characteristic dramatically affects the phase separation of the copolymers by modifying their overall hydrophobicity.