caa a22 4500 477125905 CHVBK 20180405111649.0 cr unu---uuuuu 170330e19970601xx s 000 0 eng 10.1023/A:1012142204132 doi (NATIONALLICENCE)springer-10.1023/A:1012142204132 The Stabilization and Encapsulation of Human Growth Hormone into Biodegradable Microspheres [Elektronische Daten] [OluFunmi Johnson, Warren Jaworowicz, Jeffrey Cleland, Leonie Bailey, Margarita Charnis, Eileen Duenas, Chichih Wu, Douglas Shepard, Sheila Magil, Thomas Last, Andrew Jones, Scott Putney] Purpose. To produce and evaluate sustained-acting formulations of recombinant human growth hormone (rhGH) made by a novel microencapsulation process. Methods. The protein was stabilized by forming an insoluble complex with zinc and encapsulated into microspheres of poly (D,L-lactide co-glycolide) (PLGA) which differed in polymer molecular weight (8−3 1kD), polymer end group, and zinc content. The encapsulation procedure was cryogenic, non-aqueous, and did not utilize surfactants or emulsification. The rhGH extracted from each of these microsphere formulations was analyzed by size-exclusion, ion-exchange and reversed-phase chromatography, SDS-polyacrylamide gel electrophoresis, peptide mapping, and cell proliferation of a cell line expressing the hGH receptor. In addition, the in vivorelease profile was determined after subcutaneous administration of the microspheres to rats and juvenile rhesus monkeys. Results. Protein and bioactivity analyses of the rhGH extracted from three different microsphere formulations showed that the encapsulated protein was unaltered relative to the protein before encapsulation. In vivo, microsphere administration to rats or monkeys induced elevated levels of serum rhGH for up to one month, more than 20-fold longer than was induced by the same amount of protein injected subcutaneously as a solution. The rate of protein release differed between the three microsphere formulations and was determined by the molecular weight and hydrophobicity of the PLGA. The serum rhGH profile, after three sequential monthly doses of the one formulation examined, was reproducible and showed no dose accumulation. Conclusions. Using a novel process, rhGH can be stabilized and encapsulated in a solid state into PLGA microspheres and released with unaltered properties at different rates. Plenum Publishing Corporation, 1997 sustained-release nationallicence microencapsulation nationallicence microspheres nationallicence human growth hormone nationallicence poly (lactide co -glycolide) nationallicence PLGA nationallicence Johnson OluFunmi Alkermes, Inc., 64 Sidney St., 02139, Cambridge, Massachusetts aut Jaworowicz Warren Alkermes, Inc., 64 Sidney St., 02139, Cambridge, Massachusetts aut Cleland Jeffrey Genentech, Inc., 460 Pt. San Bruno Blvd., 94080, South San Francisco, California aut Bailey Leonie Alkermes, Inc., 64 Sidney St., 02139, Cambridge, Massachusetts aut Charnis Margarita Alkermes, Inc., 64 Sidney St., 02139, Cambridge, Massachusetts aut Duenas Eileen Genentech, Inc., 460 Pt. San Bruno Blvd., 94080, South San Francisco, California aut Wu Chichih Alkermes, Inc., 64 Sidney St., 02139, Cambridge, Massachusetts aut Shepard Douglas Alkermes, Inc., 64 Sidney St., 02139, Cambridge, Massachusetts aut Magil Sheila Alkermes, Inc., 64 Sidney St., 02139, Cambridge, Massachusetts aut Last Thomas Alkermes, Inc., 64 Sidney St., 02139, Cambridge, Massachusetts aut Jones Andrew Genentech, Inc., 460 Pt. San Bruno Blvd., 94080, South San Francisco, California aut Putney Scott Alkermes, Inc., 64 Sidney St., 02139, Cambridge, Massachusetts aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/6(1997-06-01), 730-735 0724-8741 14:6<730 1997 14 11095 https://doi.org/10.1023/A:1012142204132 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012142204132 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Johnson OluFunmi Alkermes, Inc., 64 Sidney St., 02139, Cambridge, Massachusetts aut NATIONALLICENCE 700 1- Jaworowicz Warren Alkermes, Inc., 64 Sidney St., 02139, Cambridge, Massachusetts aut NATIONALLICENCE 700 1- Cleland Jeffrey Genentech, Inc., 460 Pt. San Bruno Blvd., 94080, South San Francisco, California aut NATIONALLICENCE 700 1- Bailey Leonie Alkermes, Inc., 64 Sidney St., 02139, Cambridge, Massachusetts aut NATIONALLICENCE 700 1- Charnis Margarita Alkermes, Inc., 64 Sidney St., 02139, Cambridge, Massachusetts aut NATIONALLICENCE 700 1- Duenas Eileen Genentech, Inc., 460 Pt. San Bruno Blvd., 94080, South San Francisco, California aut NATIONALLICENCE 700 1- Wu Chichih Alkermes, Inc., 64 Sidney St., 02139, Cambridge, Massachusetts aut NATIONALLICENCE 700 1- Shepard Douglas Alkermes, Inc., 64 Sidney St., 02139, Cambridge, Massachusetts aut NATIONALLICENCE 700 1- Magil Sheila Alkermes, Inc., 64 Sidney St., 02139, Cambridge, Massachusetts aut NATIONALLICENCE 700 1- Last Thomas Alkermes, Inc., 64 Sidney St., 02139, Cambridge, Massachusetts aut NATIONALLICENCE 700 1- Jones Andrew Genentech, Inc., 460 Pt. San Bruno Blvd., 94080, South San Francisco, California aut NATIONALLICENCE 700 1- Putney Scott Alkermes, Inc., 64 Sidney St., 02139, Cambridge, Massachusetts aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/6(1997-06-01), 730-735 0724-8741 14:6<730 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer