Multivesicular liposome (DepoFoam) technology for the sustained delivery of insulin-like growth factor-I (IGF-I).
Insulin-like Growth Factor I (IGF-I), a 7.65 kD protein which has a variety of metabolic functions, is being evaluated for its therapeutic benefit in several disease states. To sustain therapeutic blood levels in a number of these instances, IGF-I needs to be administered repeatedly. The objective of these studies was the development of a sustained-release depot delivery system for this protein which would replace repeated administration. Using a multivesicular liposome drug delivery system (DepoFoam), sustained delivery kinetics have been observed for IGF-I. IGF-I was successfully encapsulated in this system with good efficiency. The integrity of the encapsulated protein was maintained, as characterized by physiochemical (HPLC, SDS-PAGE), and by biological methods (mitogenic activity). The DepoIGF-I particles were also characterized by their morphology (particles were smooth, multivesicular, and there was no debris), particle size (ranged from 18 to 20 microm), and in vitro and in vivo release kinetics of IGF-I. The DepoIGF-I particles released the protein drug in a sustained manner both in vitro and in vivo without a rapid initial release, and the released protein maintained its structural integrity and biological activity. The in vitro studies in human plasma at 37 degreesC showed that the DepoIGF-I particles released IGF-I slowly over several days; 70-80% of the protein was released in 6-7 days. In a pharmacokinetic in vivo study, after subcutaneous injections in rats, IGF-I levels were sustained for 5-7 days with DepoIGF-I formulation, whereas IGF-I in the free form was cleared in 1 day. DepoFoam technology provides a pharmaceutically useful system of sustained delivery for proteins, which can be extended to other therapeutic macromolecules.
Katre
N V
NV
DepoTech Corporation, 10450 Science Center Drive, San Diego, California 92121 and Chiron Corporation, 4560 Horton Street, Emeryville, California 94608, USA. nandini_katre@depotech.com
Asherman
J
J
Schaefer
H
H
Hora
M
M
D000818:Animals; D004337:Drug Carriers; D006207:Half-Life; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008081:Liposomes / Q000737:chemistry; D051381:Rats
D004337:Drug Carriers; D008081:Liposomes; D007334:Insulin-Like Growth Factor I