Catalin Nistor

A combined in vitro and in vivo study on the interactions between somatostatin and lipid-based liquid crystalline drug carriers and bilayers

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.

Self-Assembling Lipid Formulations

Encapsulation of drugs into lipid-based liquid crystalline (LC) phases offers a broadly applicable approach for the in vivo stabilization and sustained release delivery of peptides and proteins as well as small molecule drug substances. This is exemplified by the FluidCrystal® Injection depot, an adaptive drug delivery system, combining ease of manufacturing, handling, and injection, with long acting release. The system exploits specific liquid mixtures of naturally occurring polar lipids and small amounts of solvents, which upon contact with minute quantities of aqueous tissue fluids self-assemble into reversed LC phases. The resulting encapsulation of dissolved or dispersed active pharmaceutical ingredients provides a release duration from a small volume injection, which is tunable from days to months.