title: A combined in vitro and in vivo study on the interactions between somatostatin and lipid-based liquid crystalline drug carriers and bilayers.
abstract: Somatostatin (SST) is a peptide hormone active in the regulation of the endocrine system via different somatostatin receptors subtypes. It inhibits the release of multiple secondary peptide hormones, affecting neurotransmission and cell proliferation. SST has a high therapeutic potential in the treatment of disease, such as acromegali, acute pancreatitis and gastroenteropathic endocrine tumors. However, its practical use is hampered by a short in vivo half-life of only a few minutes in man. For this reason more long-lived SST analogues, including octreotide and lanreotide, have been developed. Here we have used native SST as a model compound for a different approach of extending plasma half-lives of in vivo labile biomolecules. Through association of the peptide hormone with lipid-based liquid crystalline nanoparticle (LCNP) carriers, the terminal half-life of SST injected intravenously in rats is shown to be significantly extended from less than 10min to more than 1h. The effect on the in vivo circulation behavior depends on the mode of peptide association to the lipid particles and related physicochemical properties are discussed on the basis of in vitro light scattering, z-potential and adsorption measurements. It is concluded that application of the LCNP delivery system represents an interesting alternative to chemical modifications of in vivo sensitive therapeutically interesting peptides.
authors.affiliation: Camurus, Ideon Science Park, Sölvegatan 41, SE-223 70 Lund, Sweden.
authors.forename: Camilla
authors.initials: C
authors.lastname: Cervin
authors.forename: Pauline
authors.initials: P
authors.lastname: Vandoolaeghe
authors.forename: Catalin
authors.initials: C
authors.lastname: Nistor
authors.forename: Fredrik
authors.initials: F
authors.lastname: Tiberg
authors.forename: Markus
authors.initials: M
authors.lastname: Johnsson
mesh_terms: D000327:Adsorption; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers; D066298:In Vitro Techniques; D008051:Lipid Bilayers; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013004:Somatostatin / Q000008:administration & dosage* / Q000097:blood; D013056:Spectrophotometry, Ultraviolet; D014462:Ultrafiltration
chemical_list: D004337:Drug Carriers; D008051:Lipid Bilayers; D013004:Somatostatin