Zoya Shprakh has her expertise in pharmaceutical and analytical development of innovative antitumor drugs. She is also expert in preclinical and clinical studies. She researched and organized few Russian antitumor drugs manufacture.
Statement of the Problem: Neuroendocrine tumors are rare human tumors, which may arise in various tissue and organs. These tumors are characterized by secondary symptoms because of metabolically active substance production. Biotherapy with somatostatin analogues (SA) (Octreotide, Lanreotide, etc.) is now the standard of neuroendocrine tumors treatment. We synthesized new SA substance which is different from well-known by its structure (it is linear) and properties (insoluble in water) and investigated its pharmacological and technological characteristics. The purpose of this study was to create different dosage forms of SA to achieve the best bioavailability and efficiency. Methodology & Theoretical Orientation: SA tablets were prepared with starch, lactose, povidone, microcrystalline cellulose, etc. by wet granulation method. A lipid film rehydration method modified for hydrophobic substances was used to obtain SA liposomes. Findings: The best tablet formulation including povidone has characteristics corresponding to requirements of PhEu: desintegration time less than 15 min, resistance to crushing more than 30 N, weight variation ˂7,5 %, active substance content closed to nominal and consistent SA distribution in the batch. The liposomes with appropriate specifications that included egg lecithin and PEG-2000-DSPE were prepared and characterized by partical size (151±11 nm), pH of the liposomal dispersion (7,2±0,2) and content of somatostatin and AS incorporated in the liposomal bilayer (96±1.6 %). Study of antitumor efficacy was performed on mice transplanted tumor model, mammary adenocarcinoma Ca-755 by oral administration of SA tablets and intravenous administration of liposomal SA. It was found that tablet SA in dose 5 mg showed 85 % tumor growth inhibition (TGI) and liposomal SA in dose of 5 mg/kg 69 % TGI was obtained. Conclusion & Significance: New SA antitumor action more complete realizes by oral administration. because of SA slow fermentative degradation in gastric fluid and active ingredient release and absorption.
Elena A. Vasileva is Junior Researcher in the Laboratory of the Chemistry of Natural Quinonoid Compounds, G. B. Elyakov Pacific Institute of Bioorganic Chemistry, Vladivostok, Russia. She has an experience in identification, isolation and structure elucidation of natural quinonoid compounds from plants, their cell cultures and sea urchins.
Secondary metabolites specific to sea urchins are known as spinochromes. The most well-known sea urchin pigment echinochrome A exhibit a wide range of pharmacological activities, for example antioxidant, anti-diabetic , anti-allergic , cardioprotective , and also protects mitochondrial functions against cardiotoxic drugs . In addition, echinochrome A is the active substance in the cardioprotective and ophthalmic drug Histochrome®, produced in Russia from the sand dollar Scaphechinus mirabilis . One of the main obstacles to the wide use of echinochrome A is its insolubility in water. Histochrome is available only in ampoules in the form of echinochrome A sodium salts for intravenous injections. To expand area of echinochrome A application, it is very important to investigate abilities of echinochrome A to form complexes with substances that can increase its solubility, protect its hydroxyl groups from oxidation, preserving or enhancing its pharmacological properties. Very recently, we obtained a powder composition of echinochrome A (Ech) with other well-known antioxidants – ascorbic acid (Asc) and alpha-tocopherol (Toc). Ratio of components was chosen based on the results of lipids peroxidation inhibition assay. The most strong antioxidant effect demonstrated composition Ech-Asc-Toc 5:5:1 . We established that this composition containing bulk media is stable for 1 year and that addition of antioxidants and excipients does not affect echinochrome A permeability through artificial membrane imitating gastrointestinal tract (PAMPA assay). The developed composition showed in vitro antiviral activity against RNA-containing tick-borne encephalitis virus and DNA-containing herpes simplex virus type 1 . The studied composition of antioxidants exhibits more potent antioxidant and antiviral properties than Ech itself, thus opening perspectives of its medical application as tablets and capsules. This study was supported by the grant of the Ministry of Science and Higher Education of Russian Federation (project RFMEFI61317X0076).