Controlled release of polypeptides from polyanhydrides.
The effects of both polymer hydrophobicity and addition of stabilizers on the release and integrity of polymer-encapsulated proteins were studied. By using very hydrophobic poly[1,3-bis(p-carboxyhydroxy)hexane anhydride] with sucrose as an excipient, both recombinant bovine somatotropin and zinc insulin were released intact over 3 weeks. The released proteins appeared to maintain their integrity as judged by acidic reverse-phase HPLC, size-exclusion HPLC, radioimmunoassay, and conformation-sensitive immunoassays. Our results also suggest how polymer hydrophobicity can be used to enhance protein stability.
Ron
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E
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge 02138.
Turek
T
T
Mathiowitz
E
E
Chasin
M
M
Hageman
M
M
Langer
R
R
D000818:Animals; D002417:Cattle; D003652:Decanoic Acids; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D013006:Growth Hormone; D007118:Immunoassay; D007202:Indicators and Reagents; D007328:Insulin; D007700:Kinetics; D011091:Polyesters; D011994:Recombinant Proteins; D013055:Spectrophotometry, Infrared; D013997:Time Factors
D003652:Decanoic Acids; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007202:Indicators and Reagents; D007328:Insulin; D011091:Polyesters; D011994:Recombinant Proteins; C081012:poly(1,3-bis(4-carboxyhydroxy)hexane anhydride); D013006:Growth Hormone; C055401:decanedioic acid-4,4'-(1,3-propanediylbis(oxy))bis(benzoic acid) copolymer