ADSORPTION OF SALMON-CALCITONIN TO PLGA MICROSPHERES

Purpose. The interaction of salmon calcitonin (sCT) and poly (d,l-lact ide-co-glycolide) was detected during preparation and evaluation of mi crospheres. The purpose of this study was to quantitate the extent and nature of the interaction. Methods. Blank microspheres were prepared by an aqueous emulsification solvent extraction technique. Adsorption studies were carried out at six concentrations of sCT and three concen trations of microspheres. Adsorption isotherms were constructed using the Langmuir and Freundlich treatments. Results. Adsorption at 1 mg/ml sCT concentration resulted in almost complete depletion of the peptid e from the adsorption medium with the time to reach maximum adsorption decreasing with increasing microsphere concentration. At sCT concentr ations below 100 mu g/ml, a true equilibrium occurred in 1 hour or les s while at higher concentrations (up to 350 mu g/ml), a transient equi librium was reached in 1 to 2 hours, followed by further adsorption of the peptide. The adsorption followed the Langmuir isotherm at concent rations below 200 mu g/ml, indicating formation of a monolayer. Multil ayer interaction, described by the Freundlich isotherm, occurred at hi gher concentrations and resulted in complete depletion of sCT from the adsorption medium. The affinity constant during monolayer formation w as 0.09 and the plateau surface concentration was 5.1 mu g/mg. The mul tilayer peptide-peptide adsorption showed a lower affinity (0.025) but higher capacity (24 mu g/mg) than the monolayer peptide-polymer adsor ption. Conclusions. The results show that poly (d,l-lactide-co-glycoli de) microspheres have a high adsorption capacity for sCT which must be considered in formulating a controlled delivery product of this pepti de.