Effect of Lipid Composition of Liposomes on Biodisposition of Indomethacin in Arthritic Rats
Authors: Srinath P.1; Vyas S.P.2; Diwan P.V.1
Source: Pharmacy and Pharmacology Communications, Volume 5, Number 5, May 1999 , pp. 339-344(6)
Publisher: Pharmaceutical Press
Abstract:
A series of liposomes of indomethacin using various phospholipids (phosphatidyl choline (PC), phosphatidyl ethanolamine (PE), phosphatidyl glycerol (PG), stearylamine (SA) and cholesterol (CH)) was prepared. The effect of lipid composition on biodisposition of indomethacin was studied in arthritic rats.
The greatest encapsulation efficiency (32% ) was achieved with PC
CH
SA (1
0·5
0·1 molar ratio) liposomes. Inclusion of cholesterol did not increase encapsulation of indomethacin in the liposomes. As indomethacin is an acidic drug, inclusion of stearyl-amine, a cationic lipid, might have improved encapsulation because of electrostatic interactions.
The concentration of free indomethacin in blood, liver, spleen, kidney, brain and paw, after intravenous administration, was measured at various time points. Cmax in the liver was achieved 1 h after the administration of free drug but was delayed for up to 4 h with the encapsulated form. Localization in the liver was greatest with a PC
CH
PG (1
0·5
0·2 molar ratio) liposome formulation. Detectable concentrations of the drug in the inflammatory tissue were found for up to just 2 h with free indomethacin. With liposomal formulations detectable levels of the drug were observed even after 24 h and liposomes comprising PC
CH
PG (1
0·5
0·2) showed the greatest localization in the inflammatory tissue.
The results suggest that PC
CH
PG (1
0·5
0·2) is the optimum liposome composition for targeting arthritic joints.
Language: English
Document Type: Research article
Affiliations: 1: Pharmacology Division, Indian Institute of Chemical Technology, Hyderabad500 007, diwan@iict.ap.nic.in 2: Department of Pharmaceutical Sciences, Dr H. S. Gour Vishwavidyalaya, Sagar 470 003, India *

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