DepoFoam technology: a vehicle for controlled delivery of protein and peptide drugs.
A major challenge in the development of sustained-release formulations for protein and peptide drugs is to achieve high drug loading sufficient for prolonged therapeutic effect coupled with a high recovery of the protein/peptide. This challenge has been successfully met in the formulation of several peptide and protein drugs using the DepoFoam, multivesicular lipid-based drug delivery system. DepoFoam technology consists of novel multivesicular liposomes characterized by their unique structure of multiple non-concentric aqueous chambers surrounded by a network of lipid membranes. The objective of this paper is to demonstrate that DepoFoam technology can be used to develop sustained-release formulations of therapeutic proteins and peptides with high loading. DepoFoam formulations of a protein such as insulin, and peptides such as leuprolide, enkephalin and octreotide have been developed and characterized. The data show that these formulations have high drug loading, high encapsulation efficiency, low content of free drug in the suspension, little chemical change in the drug caused by the formulation process, narrow particle size distribution, and spherical particle morphology. Drug release assays conducted in vitro in biological suspending media such as human plasma indicate that these formulations provide sustained release of encapsulated drug over a period from a few days to several weeks, and that the rate of release can be modulated. In vivo pharmacodynamic studies in rats also show a sustained therapeutic effect over a prolonged period. These results demonstrate that the DepoFoam system is capable of efficiently encapsulating therapeutic proteins and peptides and effectively providing controlled delivery of these biologically active macromolecules.
Ye
Q
Q
DepoTech Corporation, 10450 Science Center Drive, San Diego, CA 92121, USA.
Asherman
J
J
Stevenson
M
M
Brownson
E
E
Katre
N V
NV
D000818:Animals; D001798:Blood Proteins / Q000032:analysis; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D004745:Enkephalins / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry; D016729:Leuprolide / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry / Q000493:pharmacokinetics*; D018613:Microscopy, Confocal; D015282:Octreotide / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry; D010316:Particle Size; D010455:Peptides / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry; D011506:Proteins / Q000008:administration & dosage / Q000737:chemistry; D051381:Rats; D011994:Recombinant Proteins; D013997:Time Factors
D001798:Blood Proteins; D003692:Delayed-Action Preparations; D004745:Enkephalins; D007328:Insulin; D008081:Liposomes; D010455:Peptides; D011506:Proteins; D011994:Recombinant Proteins; D016729:Leuprolide; D015282:Octreotide