Abstract

A new pentapeptide analogue of somatostatin was synthesized and preliminary studies demonstrated that this analogue possessed antitumor activity on transplanted solid tumors of mice. Due the analogue’s insolubility in water, a liposomal formulation was attempted to increase bioavailability of the drug, to administer intravenously and to improve selectivity towards the tumor cells. This study employed the somatostatin analogue, egg lecithin, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000, cholesterol and sucrose. Model compositions of the somatostatin analogue liposomal dosage form were prepared using the lipid film rehydration method. All samples obtained were characterized by measuring size of liposomes, pH of the liposomal dispersion, and assay of somatostatin analogue incorporated in the liposomal bilayer. Efficiency of the formulation was investigated on models of breast adenocarcinoma Ca-755. During experimental development of the somatostatin analogue liposomal formulation, an optimal composition was established, which included egg lecithin and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000 in the 72/1 molar ratio. Influence of extrusion on the quality of liposomal preparations was studied. It was shown that to reach an optimal liposome size of about 150 nm, 7 extrusion cycles were necessary. In addition, while assessing the stability of the somatostatin analogue liposomal dispersion during storage it was found that somatostatin analogue was extremely unstable in liquid form, thus, to produce a stable formulation, lyophilization became necessary. The liposomal formulation when tested on transplanted tumors in mice, more than 60 % tumor growth inhibition was observed at 5 mg/kg dose and more than 80 % tumor growth inhibition at 20 mg/kg dose. These findings indicated that further efforts are required to improve this liposomal formulation to develop the somatostatin analogue in to a potential antitumor drug.