The Entrapment of Somatostatin in a Lipid Formulation: Retarded Release and Free Radical Reactivity

Abstract

The natural peptide somatostatin has hormonal and cytostatic effects exerted by the binding to specific receptors in various tissues. Therapeutic uses are strongly prevented by its very short biological half-life of 1–2 min due to enzymatic hydrolysis, therefore encapsulation methodologies are explored to overcome the need for continuous infusion regimes. Multilamellar liposomes made of natural phosphatidylcholine were used for the incorporation of a mixture of somatostatin and sorbitol dissolved in citrate buffer at pH = 5. Lyophilization and reconstitution of the suspension were carried out, showing the flexibility of this preparation. Full characterization of this suspension was obtained as particle size, encapsulation efficiency and retarded release properties in aqueous medium and human plasma. Liposomal somatostatin incubated at 37 °C in the presence of Fe(II) and (III) salts were used as a biomimetic model of drug-cell membrane interaction, evidencing the free radical processes of peroxidation and isomerization that transform the unsaturated fatty acid moieties of the lipid vesicles. This study offers new insights into a liposomal delivery system and highlights molecular reactivity of sulfur-containing drugs with its carrier or biological membranes for pharmacological applications.