caa a22 4500 477127126 CHVBK 20180405111653.0 cr unu---uuuuu 170330e19971001xx s 000 0 eng 10.1023/A:1012176823155 doi (NATIONALLICENCE)springer-10.1023/A:1012176823155 Characterization of Poly(glycolide-co-D,L-lactide)/Poly(D,L-lactide) Microspheres for Controlled Release of GM-CSF [Elektronische Daten] [Dean Pettit, J. Lawter, W. Huang, Susan Pankey, Nancy Nightlinger, David Lynch, Jo Schuh, Philip Morrissey, Wayne Gombotz] Purpose. This study describes the preparation and characterization of a controlled release formulation of granulocyte-macrophage colony-stimulating factor (GM-CSF) encapsulated in poly(glycolide-co-D,L-lactide) (PLGA) and poly(D,L-lactide) (PLA) microspheres. Methods. GM-CSF was encapsulated in PLGA/PLA microspheres by a novel silicone oil based phase separation process. Several different blends of PLGA and low molecular weight PLA were used to prepare the microspheres. The microspheres and the encapsulated GM-CSF were extensively characterized both in vitroand in vivo. Results. Steady release of GM-CSF was achieved over a period of about one week without significant 'burst' of protein from the microspheres. Analysis of microsphere degradation kinetics by gel permeation chromatography (GPC) indicated that low molecular weight PLA enhanced the degradation of the PLGA and thereby affected release kinetics. GM-CSF released from the microspheres was found to be biologically active and physically intact by bioassay and chromato-graphic analysis. Analysis of serum from mice receiving huGM-CSF indicated that the GM-CSF was biologically active and that a concentration of greater than 10 ng/mL was maintained for a period lasting at least nine days. MuGM-CSF was not detected followingin vivo administration of muGM-CSF microspheres. The tissues of mice receiving muGM-CSF microspheres were characterized by infiltration of neutrophils, and macrophages which were in significant excess of those found in mice administered with placebo controls (i.e. microspheres without GM-CSF). Conclusions. This study demonstrates the influence of formulation parameters on the encapsulation of GM-CSF in PLGA/PLA microspheres and its controlled release in biologically active form. The intense local tissue reaction in mice to muGM-CSF microspheres demonstrates the importance of the mode of delivery on the pharmacologic activity of GM-CSF. Plenum Publishing Corporation, 1997 poly(glycolide-co-D,L-lactide) nationallicence poly(D,L-lactide) nationallicence granulocyte-macrophage colony-stimulating factor (GM-CSF) nationallicence biodegradable microspheres nationallicence pharmacokinetics nationallicence resorbable polymer nationallicence Pettit Dean Department of Analytical Chemistry and Formulation, Immunex Corporation, 9810, Seattle, Washington aut Lawter J. Chemical and Pharmaceutical Development, Wyeth-Ayerst Research, Pearl River, 98195, New York aut Huang W. Chemical and Pharmaceutical Development, Wyeth-Ayerst Research, Pearl River, 98195, New York aut Pankey Susan Department of Analytical Chemistry and Formulation, Immunex Corporation, 9810, Seattle, Washington aut Nightlinger Nancy Department of Analytical Chemistry and Formulation, Immunex Corporation, 9810, Seattle, Washington aut Lynch David Department of Immunobiology, Immunex Corporation, 98101, Seattle, Washington aut Schuh Jo Department of Molecular Immunology, Immunex Corporation, 98101, Seattle, Washington aut Morrissey Philip Department of Molecular Immunology, Immunex Corporation, 98101, Seattle, Washington aut Gombotz Wayne Department of Analytical Chemistry and Formulation, Immunex Corporation, 9810, Seattle, Washington aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/10(1997-10-01), 1422-1430 0724-8741 14:10<1422 1997 14 11095 https://doi.org/10.1023/A:1012176823155 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012176823155 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Pettit Dean Department of Analytical Chemistry and Formulation, Immunex Corporation, 9810, Seattle, Washington aut NATIONALLICENCE 700 1- Lawter J. Chemical and Pharmaceutical Development, Wyeth-Ayerst Research, Pearl River, 98195, New York aut NATIONALLICENCE 700 1- Huang W. Chemical and Pharmaceutical Development, Wyeth-Ayerst Research, Pearl River, 98195, New York aut NATIONALLICENCE 700 1- Pankey Susan Department of Analytical Chemistry and Formulation, Immunex Corporation, 9810, Seattle, Washington aut NATIONALLICENCE 700 1- Nightlinger Nancy Department of Analytical Chemistry and Formulation, Immunex Corporation, 9810, Seattle, Washington aut NATIONALLICENCE 700 1- Lynch David Department of Immunobiology, Immunex Corporation, 98101, Seattle, Washington aut NATIONALLICENCE 700 1- Schuh Jo Department of Molecular Immunology, Immunex Corporation, 98101, Seattle, Washington aut NATIONALLICENCE 700 1- Morrissey Philip Department of Molecular Immunology, Immunex Corporation, 98101, Seattle, Washington aut NATIONALLICENCE 700 1- Gombotz Wayne Department of Analytical Chemistry and Formulation, Immunex Corporation, 9810, Seattle, Washington aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/10(1997-10-01), 1422-1430 0724-8741 14:10<1422 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer