Timo Laakso

Cellular distribution in rat liver of intravenously administered polyacryl starch and chondroitin sulfate microparticles

Abstract The interaction of polyacryl starch and chondroitin sulfate (CS) microparticles with rat liver cells was studied in vivo and in cell cultures. Kupffer cells (KC) in culture avidly engulfed both starch and CS particles. Cultured liver endothelial cells (LEC) bound CS, and to a lesser degree starch particles. Parenchymal cells (PC) in culture did not bind any of the particles. I.v. injection of either type of particles labelled with fluorescein isothiocyanate, and subsequent isolation of the liver cells showed uptake only in KC. After i.v. administration of 14 C-labelled particles, radioactivity was accumulated mainly in KC. Thus, polysaccharide microparticles in the μm range may be suitable for targeting drugs to KC.

Biodegradable microspheres. VIII. Killing of Leishmania donovani in cultured macrophages by microparticle-bound primaquine

Primaquine covalently bound to polyacryl starch microparticles has been shown to kill Leishmania donovani in cultured mouse peritoneal macrophages. The drug was derivatized with a tetrapeptide spacer and the derivative (Ala-Leu-Ala-Leu-PQ) coupled to the microparticles. This drug-carrier complex did not kill free promastigotes in suspension, but was effective against amastigotes in cultured mouse peritoneal macrophages. These results show that lysosomal processing of the drug-carrier complex is necessary in order to liberate the pharmacologically active drug. Also, the possible role of reactive oxygen intermediates for the anti-leishmanial effect was studied.

Development of mass transport resistance in poly(lactide-co-glycolide) films and particles - A mechanistic study.

Poly(D,L-lactide-co-glycolide) (PLG) is the most frequently used biodegradable polymer in the controlled release of an encapsulated drug. The purpose of this work was to explain the surprisingly slow diffusion through this polymer, and locate the major source of mass transport resistance. Diffusion of human growth hormone (hGH) and glucose through PLG films was undetectable (using a diffusion cell), although the degraded polymer contained several times more water than polymer mass. In vitro release of hGH from PLG-coated particles also showed a surprisingly slow rate of release. Non-porous regions inside the PLG films were detected after three weeks of degradation using dextran-coupled fluorescent probes and confocal microscopy. The findings were supported by scanning electron microscopy. Diffusion through PLG films degraded for five weeks was significantly increased when the porosity of both surfaces was increased due to the presence of ZnCl(2) in the buffer the last 3 days of the degradation period. The results indicated high mass transport resistance inside the films after three weeks of degradation, and at the surfaces after five weeks of degradation. These results should also be applicable to microparticles of different sizes. Knowledge of the reason for transport resistance is important in the development of pharmaceuticals and when modifying the rate of drug release.