Recombinant human erythropoietin (rhEPO) loaded poly(lactide-co-glycolide) microspheres: influence of the encapsulation technique and polymer purity on microsphere characteristics.
Recombinant human erythropoietin (EPO) and fluorescein isothiocyanate-labelled dextran (FITC-dextran) loaded biodegradable microspheres were prepared from poly(lactide-co-glycolide) (PLG) by a modified spray-drying technique. This microencapsulation method was compared with the water-in-oil-in-water (w/o/w) double-emulsion method. As expected, microsphere morphology, particle size and particle size distribution strongly depended on the production process. The spray-drying method was found to have a number of advantages compared to the w/o/w double-emulsion technique. The content of residual dichloromethane (DCM) in the final product was significantly lower in case of the microspheres prepared by spray-drying. Concerning EPO loaded microspheres, spray-drying yielded higher encapsulation efficiencies. Although the microspheres obtained by spray-drying are subjected to intensive mechanical and thermal stress during the preparation, the amount of aggregates of EPO in PLG microspheres were not increased compared to the w/o/w technique. Depending on the manufacturing method, addition of cyclic DL-lactide dimers (referred to as monomers in the following) affected the in vitro release profiles of EPO and FITC-dextran from PLG microspheres. Using differential scanning calorimetry it was shown that these low molecular weight substances only seem to be present inside the microspheres produced by spray-drying. DL-Lactide significantly reduced the initial burst release of both EPO and FITC-dextran. While the following release period of EPO was not affected by the DL-lactide content, a more linear FITC-dextran release pattern could be achieved. It can be concluded that the spray-drying technique provides a number of advantages compared to the w/o/w method. The modulation of protein release using low molecular weight additives is of particular interest for parenteral depot systems.
Bittner
B
B
Philipps-University, Marburg, Germany.
Morlock
M
M
Koll
H
H
Winter
G
G
Kissel
T
T
D002152:Calorimetry, Differential Scanning; D003911:Dextrans; D004339:Drug Compounding; D004355:Drug Stability; D004921:Erythropoietin / Q000008:administration & dosage* / Q000737:chemistry*; D016650:Fluorescein-5-isothiocyanate; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D008970:Molecular Weight; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D011994:Recombinant Proteins; D012997:Solvents
D003911:Dextrans; D011108:Polymers; D011994:Recombinant Proteins; D012997:Solvents; D004921:Erythropoietin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D016650:Fluorescein-5-isothiocyanate