Multivesicular Liposome (DepoFoam) Technology for the Sustained Delivery of Insulin-Like Growth Factor-I (IGF-I)

Abstract

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.

Effect of ampicillin and chloroquine on humoral immune response elicited by bovine albumin encapsulated in liposomes

“…Hence, the formulation stored at 4 ± 0.5°C demonstrated a very low antigen leakage compared to the formulation stored at 25 ± 0.5°C and 37 ± 0.5°C, respectively, suggesting that refrigerated conditions are well suited to the developed formulation. It was demonstrated previously in a long-term storage stability study that liposomes were stable for over 1 year (17). …”

Multivesicular liposome formulations for the sustained delivery of ropivacaine hydrochloride: Preparation, characterization, and pharmacokinetics

“…Only breaches in the outermost membranes of an MVL result in release of encapsulated drug to the external medium, and release of drug from the internal vesicles results in a redistribution of drug inside the particle instead of drug release from the particle (Kim et al, 1996;Spector & Zasadzinski, 1996;Katre et al, 1998;Langston et al, 2003;Jain et al, 2005). The interconnected network of the multi-vesiculated structure also ensures that the vesicles can rearrange themselves internally without release of drug by internal fusion and division.…”

Lipid Carriers: A Versatile Delivery Vehicle for Proteins and Peptides

“…18) Furthermore, MVLs as depofoam particles were stable for 1 year at 4°C in a long-term storage stability study. 19) In a recent work by Langston, et al, 20) Leridistim (a protein from the MPO family) was encapsulated in multivesicular liposomes (Depo Foam TM ) for sustained delivery, and a single injection of Leridistim MVLs was demonstrated to result in elevated neutrophil counts for 10 days, in contrast to only 2 days for un-encapsulated Leridistim.…”