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Article # : SC14

Sema alış, Ph.D.



Adsorption of Salmon Calcitonin to PLGA Microspheres


Sema Calis,1 Ramasubbu Jeyanthi,2 Tsuimin Tsai,3 Rahul C. Mehta, and Patrick P. DeLuca4,5


1 Present address: Faculty of Pharmcy. Hacetlcpe University, Hacettepe, 06100 Ankara, Turkey

Oravax, Inc., Department of Dental Research, Bidg. 2832 Ernie Pyle Road, Fort Meade. Maryland 20755.

School of Pharmacy, Taipei Medical College. 250Wu-Hsing Street, Taipei. Taiwan.

4 College of Pharmacy, University of Kentucky, Lexington, Kentucky 40536-0082.

5 To whom correspondence should be addressed.




The interaction of salmon calcitonin (sCT) and poly (d,l-laetide-co-glycolide) was detected during preparation and evaluation of microspheres. 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 concentrations of microspheres. Adsorption^isotherms were constructed using the Langmuir and Freundlich treatments. Results. Adsorption at I mg/ml sCT concentration resulted in almost complete depletion of the peplide from the adsorption medium with the time to reach maximum adsorption decreasing with increasing microsphere concentration. At sCT concentrations below100 mg/ml, a true equilibrium occurred in 1 hour or less while at higher concentrations (up to 350 p-g/ml), a transient equilibrium was reached in 1 to 2 hours, followed by further adsorption of the peptide. The adsorption followed the Langnuir isotherm at concentrations below 200 (Jig/mi, indicating formation of a monolayer. Multilayer interaction, described by (he Freundlich isotherm, occurred at higher concentrations and resulted in complete depletion of sCT from the adsorption medium. The affinity constant during monolayer formation was 0.09 and the plateau surface concentration was 5.1 Hg/mg. The multilayer peptide-pcplide adsorption showed a iower affinity (0.025) but higher capacity (24 p.g/mg than the monolayer peptide-polymer adsorption. Conclusions. The results show that poly (d.l-lactide-co-glycolide) microspheres have a high adsorption capacity for sCT which must be considered in formulating a controlled delivery product of this peplide.


Key words

Peptide-polymer interaction; salmon calcitonin; adsorption kinetics; adsorption isotherms: PLGA.