The increase of bioavailability and antiinflammatory effect of indomethacin included into phospholipid nanoparticles

Abstract

The ultrafine formulation on the base of plant phosphatidylcholine and antiinflammatory remedy indomethacin with nanoparticles less than 50 nm was obtained. Drug bioavailability after its peroral administration to rats was more than 2 fold higher as compared with free indomethacin. Increased antiinflammatory activity of indomethacin in phospholipids nanoparticles as compared with its free form was shown in two models of inflammation - adjuvant arthritis in rats and conconavalin A induced edema in mice. The increased bioavailability of indomethacin after administration of its phospholipid formulation allows to decrease a dose for achievement of therapeutic effect, that reduces risks of occurrence of collateral displays.

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

“…The phospholipid nanocomposition of indomethacin was obtained according to the procedure described [ 15 ]: 200 mL of distilled water was warmed to 45 °C and 25 g of maltose was added with stirring until completely dissolved. Then, 625 mg of indomethacin and 6.25 g of phospholipid were added to the resulting solution, homogenized and adjusted to 250 mL with distilled water.…”

“…Then, 625 mg of indomethacin and 6.25 g of phospholipid were added to the resulting solution, homogenized and adjusted to 250 mL with distilled water. The resulting coarse emulsion was passed through a homogenizer (Mini-Lab 7.3 VH, Rannie, Hirtshals Denmark) at a pressure of 800 bar for 5 cycles and filtered then through a filter with a pore size of 0.22 microns (Durapore, Merck, Darmstadt, Germany), poured into 10 mL vials and freeze-dried on a Virtis Advantage XL laboratory unit (Gardiner, New York, NY, USA), following [ 15 ]. Schematically, the process of obtaining the Indolip composition is shown in Figure 1 .…”

“…After oral administration of this phospholipid composition to rats, the increase in the bioavailability of indomethacin was twice as high compared to the free substance. Two inflammation models (adjuvant arthritis in rats and conconavalin-induced edema in mice) showed increased anti-inflammatory activity of indomethacin included into phospholipid nanoparticles compared with its free form [ 1 , 15 ]. Thus, it has been shown that the phospholipid transport nanosystem is capable of changing both the pharmacokinetics of a substance and its physical and chemical characteristics, for example, solubility.…”

Preparation and Properties of Antitumor Drug Based on Lipid Derivative of Sarcolysin

“…На примере ряда лекарств (индометацин, арбидол, рифампицин, преднизолон, доксорубицин и др.) было показано увеличение биодоступности, а в ряде случаев повышение специфической активности и снижение нежелательных побочных проявлений при их включении в наночастицы на основе растительных фосфолипидов размером до 50 нм [19][20][21][22][23]. Наиболее технологичным методом получения коллоидных наночастиц на основе фосфолипидов для дальнейшего использования их как транспортной системы, является способ гомогенизации под высоким давлением (500 -1500 атм) [24].…”

Comparison of a new nanoform of the photosensitizer chlorin e6, based on plant phospholipids, with its free form

“…The studies demonstrated that incorporation of a drug in the phospholipid nanoparticles of that size substantially affects its pharmacokinetics. For example, it certainly changes drug distribution over blood components, increases accumulation in areas of inflammation, significantly enhances bioavailability, and consequently improves efficacy of its therapeutic effect . The approaches developed by us were used to obtain a composition of Ce6 incorporated in phospholipid nanoparticles (Ce6–PC) of extremely small size (up to 30 nm) as a transport system.…”