Study of Physico-Chemical Properties and Morphology of Phospholipid Composition of Indomethacin

Nonsteroidal anti-inflammatory drugs (NSAIDs), inhibitors of cyclooxygenase-2, an enzyme involved in the formation of anti-inflammatory prostaglandin PGE2, are the most common treatment for chronic inflammatory diseases, such as, for example, arthritis. One of the most commonly used drugs of this class is indomethacin, a derivative of indolylacetic acid. In this work, we studied the physicochemical properties of the phospholipid composition of indomethacin obtained earlier (codenamed “Indolip”) and the effect of freeze drying on its parameters. It was shown that the properties such as particle size, light transmission, phospholipid oxidation index did not change significantly, which indicated the stability of the drug after lyophilization. Measurement of the spectra of small-angle neutron scattering has shown that morphologically, Indolip is a vesicle whose radius is five times greater than the value of the bilayer thickness

Drug Transport System Based on Phospholipid Nanoparticles: Production Technology and Characteristics

One of the current trends in modern pharmaceuticals is the supply of drugs by transport systems. The use of delivery systems allows to increase the therapeutic efficacy, tolerability, and safety of drug therapy. Liposomes, polymer nanoparticles, carbon nanoparticles, blood cells, metal nanoparticles, oxides, etc., are used as transport systems. This work is aimed at obtaining a finished technological product based on soy phospholipids with particle size in the nanometer range and reproducible characteristics (size, charge). For this purpose, we carried out investigations to select the optimal conditions of technological process. The developed technology makes it possible to obtain phospholipid nanoparticles without the use of any solubilizers and/or surfactants, which increases its practical relevance for further work. The versatility of the technology is demonstrated by the example of incorporation of drugs of various chemical nature and pharmacotherapeutic groups

Chlorin e6 Phospholipid Delivery System Featuring APN/CD13 Targeting Peptides: Cell Death Pathways, Cell Localization, In Vivo Biodistribution

We have previously designed a phospholipid delivery system for chlorin e6 to increase the efficacy of photodynamic therapy involving a second-generation photosensitizer. Further research into the matter led to double modification of the obtained nanoparticles with ligands exhibiting targeting and cell-penetrating effects: an NGR-containing peptide and heptaarginine (R7), respectively. This study investigated the cell death pathway on HT-1080 tumor cells after treatment with the proposed compositions: the chlorin e6 phospholipid composition and the two-peptide chlorin e6 phospholipid composition. It was demonstrated that most of the cells died by apoptosis. Colocalization analysis of chlorin e6 in the phospholipid composition with two peptides showed mitochondria are one of the targets of the photosensitizer. An HT-1080 tumor-bearing mouse model was used to evaluate the biodistribution of the drug in tumor, liver, and kidney tissues after administration of the study compositions in comparison with free chlorin e6. The photosensitizer mostly accumulated in the tumor tissue of mice administered the phospholipid compositions, and accumulation was increased 2-fold with the peptide-containing composition and approximately 1.5-fold with the unenhanced composition, as compared with free chlorin e6. The enhancement of the chlorin e6 phospholipid composition with targeting and cell-penetrating peptides was found to be effective both in vitro and in vivo