Institute of Biomedical Chemistry

Transcription

1 Russian Academy of Sciences Medical Branch Institute of Biomedical Chemistry 71 years old still alive and still creative!

2 DRUG DELIVERY SYSTEMS BASED ON THE PHOSPHOLIPIDS IN LAST 20 YEARS THE MOST SIGNIFICANT SUCCESS WAS ACHIEVED IN ELABORATION OF PHOSPHOLIPID TRANSPORT SYSTEMS, PHOSPHOLIPID NANOPARTICLES (MICELLES, LIPOSOMES), THAT HAVE TODAY A NUMBER OF PREFERENCES AS COMPARED WITH OTHERS, FOR EXAMPLE POLYMER NANOPARTICLES. IBMC has developed a unique technology for producing phospholipid nanoparticles extremely of small size with a fundamentally different morphology (Kiselev M.A. at al, Application of small-angle X-ray scattering to the characterization and quantification of the drug transport nanosystem based on the soybean phosphatidylcholine, 2015) CHOLESTEROL DRUG PHOSPHATIDYLCHOLINE

3 BASIC ADVANTAGES OF PHOSPHOLIPID DRUG DELIVERY NANOSYSTEMS The universal nature. Perhaps the inclusion of a large number of medicinal substances of different therapeutic groups. The main requirement for drug compound - hydrophobicity (poor solubility in water) and lipophilic (affinity to fats and oils) Simple structure, so the phospholipid transport nanosystems technology is reproducible on an industrial scale and has a low cost factor. Is a fine emulsion of phospholipid and nanoparticles, other than the cryoprotectant does not contain other auxiliary ingredients (emulsifiers, stabilizers, surfactants, etc.) Structure and phospholipids of extremely small size of nanoparticles can significantly increase the amount of the adsorbed and / or "embedded" drug compound, drug delivered into the cell, and to use the natural transport way in the body, for example, low-density lipoprotein, which are enriched receptors inflamed tissue.

4 DRUG DELIVERY SYSTEMS BASED ON THE PHOSPHOLIPIDS The proposed project is designed IBMC production technology ultra-thin phospholipid nanoemulsion for pharmaceutical use (Patent US A1). The technology is scaled in terms of pilot production institute and allows a single interconnected mode to receive drugs from the loading of the starting materials "input" to "output" of the finished product. The technology is based on three essential stage - homogenization pressure of 1000 bar, ultrafiltration and freeze drying Primary homogenization Homogenization Ultrafiltration Filling Freeze drying Packing THE DEVELOPED TECHNOLOGY ALLOWS US TO CREATE PHOSPHOLIPID NANOPARTICLES WITH THE SIZE OF (20 ± 2 nm) WHICH IS VERY CLOSE TO THAT CALCULATED FOR THE THERMODYNAMICALLY STABLE PARTICLES (10 nm) THE QUESTION IS: WHAT HAPPENS WITH THESE PARTICLES DURING DRUG INCORPORATION INTO THEM??

5 Volume% [linear] А 22 нм SIZE OF PHOSPHOLIPIDS NANOPARTICLES В C nm Size (nm) A - Atomic force microscopy, B - Laser-correlation analysis, c - Scanning Electron Microscopy

6 The index of inflammation reaction to Con A,% Concentration in blood, mkg/ml Concentration in blood, mkg/ml EFFICIENCY OF PHOSPHOLIPID DRUG DELIVERY SYSTEM NF-Arbidol Arbidol Time, min С max NF-Arbidol > С max Arbidol 6 times AUC 0-30 NF-Arbidol > АUC 0-30 Arbidol 8 times NF-prednisolone prednisolone Time, min. С max NF-Prednisolone > С max Prednisolone 1,6 times AUC 0-60 NF-Prednisolon > АUC 0-60 Prednisolone 5 times Сontrol Prednisolone NF-Prednisolone 2,5 mg/kg 5 mg/kg 25 mg/kg Anti-inflammatory effect of NF-Prednisolone at a dose of 2.5 mg / kg > anti-inflammatory effect of Prednisolone at a dose of 25 mg/kg 1.3 times

7 IDEAS FOR collaborators / partners Undertake research into medicinal compositions based on phospholipid nanoparticles Pre-clinical / clinical studies Re-Launch of Germany's medical and preventive drugs based on phospholipid nanoparticles

8 THANK YOU FOR ATTENTION! V.N. Orekhovich Institute of Biomedical Chemistry > 140 papers annually = 8 patents licensed in the last 10 years