INFLUENCE OF SURFACE-PROPERTIES AT BIODEGRADABLE MICROSPHERE SURFACES- EFFECTS ON PLASMA-PROTEIN ADSORPTION AND PHAGOCYTOSIS

Objective. The objective of this work was to determine plasma protein adsorption and macrophage phagocytosis of biodegradable polyanhydride. polylactic acid and polylactic-co-glycolic acid microspheres prepared by both spray-drying and solvent evaporation techniques. Methods. Mic rospheres were characterized by scanning electron microscopy (SEM), co nfocal laser microscopy, particle size distribution and zeta (zeta) po tential determination. Plasma protein adsorption onto the microspheres was determined using a fluoroaldehyde reagent. Phagocytosis was evalu ated by incubating microspheres containing the angiotensin II antagoni st, L-158,809, with the macrophages in the presence or absence of the phagocytosis inhibitor cythochalasin D. The extent of phagocytosis was established by fluorescence determination of L-158,809 and by optical microscopy. The effect of amphiphilic poly(ethylene glycol) (PEG) der ivatives on phagocytosis was determined using PEG-distearate incorpora ted into the microspheres. Results, The average diameter of the micros pheres, which depended on the polymer and the initial formulation, ran ged from 0.9 to 3.2 micrometers. zeta potential studies showed strong negative values irrespective of the polymer used for the spray-dried f ormulations. The zeta potential was masked by the incorporation of PEG 400- or PEG 1,400-distearate in the formulation. Confocal laser micro scopy showed a homogenous dispersion of PEG (measured as PEG-fluoresce in) in the microspheres. Protein adsorption was not observed for any o f the microsphere formulations following incubation with bovine serum. Incubation of microspheres with murine macrophages showed that PEG-di stearate inhibited phagocytosis at appropriate levels (0.1% w/w). High er levels >1% w/w of PEG-distearate) resulted in enhanced association with macrophages, despite the presence of the phagocytosis inhibitor c ytochalasin D, indicating fusion between the microspheres and the plas ma membrane. Conclusions. These results demonstrate that spray-dried P EG-containing microspheres can be manufactured and that an appropriate concentration of this excipient in microspheres results in decreased phagocytosis.