PURPOSE: The interaction of salmon calcitonin (sCT) and poly (d,l-lactide-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 1 mg/ml sCT concentration resulted in almost complete depletion of the peptide from the adsorption medium with the time to reach maximum adsorption decreasing with increasing microsphere concentration. At sCT concentrations below 100 micrograms/ml, a true equilibrium occurred in 1 hour or less while at higher concentrations (up to 350 micrograms/ml), a transient equilibrium was reached in 1 to 2 hours, followed by further adsorption of the peptide. The adsorption followed the Langmuir isotherm at concentrations below 200 micrograms/ml, indicating formation of a monolayer. Multilayer interaction, described by the 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 micrograms/mg. The multilayer peptide-peptide adsorption showed a lower affinity (0.025) but higher capacity (24 micrograms/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 peptide.
PURPOSE: The interaction of salmon calcitonin (sCT) and poly (d,l-lactide-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 1 mg/ml sCT concentration resulted in almost complete depletion of the peptide from the adsorption medium with the time to reach maximum adsorption decreasing with increasing microsphere concentration. At sCT concentrations below 100 micrograms/ml, a true equilibrium occurred in 1 hour or less while at higher concentrations (up to 350 micrograms/ml), a transient equilibrium was reached in 1 to 2 hours, followed by further adsorption of the peptide. The adsorption followed the Langmuir isotherm at concentrations below 200 micrograms/ml, indicating formation of a monolayer. Multilayer interaction, described by the 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 micrograms/mg. The multilayer peptide-peptide adsorption showed a lower affinity (0.025) but higher capacity (24 micrograms/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 peptide.
Authors: Amir H Ghassemi; Mies J van Steenbergen; Herre Talsma; Cornelus F van Nostrum; Daan J A Crommelin; Wim E Hennink Journal: Pharm Res Date: 2010-07-03 Impact factor: 4.200
Authors: Daniel K Yarbrough; Randal Eckert; Jian He; Elizabeth Hagerman; Fengxia Qi; Renate Lux; Ben Wu; Maxwell H Anderson; Wenyuan Shi Journal: PLoS One Date: 2011-08-15 Impact factor: 3.240
Authors: Daniel K Yarbrough; Elizabeth Hagerman; Randal Eckert; Jian He; Hyewon Choi; Nga Cao; Karen Le; Jennifer Hedger; Fengxia Qi; Maxwell Anderson; Bruce Rutherford; Ben Wu; Sotiris Tetradis; Wenyuan Shi Journal: Calcif Tissue Int Date: 2009-12-01 Impact factor: 4.333