title: Biodisposition of PEG-coated lipid microspheres of indomethacin in arthritic rats.
abstract: Conventional lipid microspheres (LM) were prepared using soybean oil and lipid at a 5.5:1 weight ratio with lipid phase consisting of PC (phosphatidyl choline):CH (cholesterol) (1:0.5) by molar ratio. The average diameter of the particles was 150 nm. Long-circulating microspheres (S-LM) were also prepared similarly but the lipid phase consisted of PC:CH:DSPE-PEG (phosphatidyl choline:cholesterol:distearoyl phosphatidyl ethanolamine-polyethylene glycol) 1:0.5:0.16 by molar ratio. A comparative biodistribution study was conducted between free indomethacin and lipo-indomethacin (LM and S-LM) in the arthritic rats by administering the formulations at a dose equivalent to 12 mg of indomethacin/kg. It was observed that the free drug as well as the encapsulated drug followed biphasic clearance from the blood. Pharmacokinetic parameters, such as AUC(0-t), terminal half-life, MRT increased significantly when the drug was used in encapsulated form (p < 0.05). Clearance of the drug was reduced 1.4 times with the conventional lipid microspheres and was reduced three-fold when encapsulated in polyethylene glycol-coated lipid microspheres. The overall drug targeting efficiency (T(e)) with the PEG-coated lipid microspheres was 7.5-fold higher than the conventional lipid microspheres. The high accumulation of the drug in arthritic paw with S-LM system may be accounted for by the reduced uptake by RES cells, and thereby, availability for extravascularization in the inflammatory tissues.
authors.affiliation: College of Pharmacy, South Dakota State University, Brookings, SD 57007, USA. Srinath_palakurthi@sdstate.edu
authors.forename: S
authors.initials: S
authors.lastname: Palakurthi
authors.forename: S P
authors.initials: SP
authors.lastname: Vyas
authors.forename: P V
authors.initials: PV
authors.lastname: Diwan
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000378:metabolism*; D001682:Biological Availability; D007213:Indomethacin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008081:Liposomes; D008297:Male; D008863:Microspheres; D011092:Polyethylene Glycols / Q000493:pharmacokinetics* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology
chemical_list: D008081:Liposomes; D011092:Polyethylene Glycols; D007213:Indomethacin