Site specific chemical delivery of NSAIDs to inflamed joints: synthesis, biological activity and gamma-imaging studies of quaternary ammonium salts of tropinol esters of some NSAIDs or their active metabolites.
Quaternized tropinol ester derivatives of some commonly used non-steroidal anti-inflammatory drugs (NSAIDs) or their active metabolites, were prepared and studied for their anti-inflammatory activity in a chronic inflammation model and for inflamed tissue tropism. The quaternized esters were radiolabeled with 99mTechnetium (99mTc) and their selective localization in the inflamed tissue was traced using scintigraphy. In the chronic arthritis rodent model, most of the quaternized esters exhibited anti-inflammatory effect comparable to their respective parent drugs. In the gamma-imaging studies only the quaternary derivatives exhibited selective accumulation into the inflamed tissue unlike the parent NSAIDs or the unquaternized tropinol esters. This work is a step ahead in the direction of use of quaternary ammonium ester derivatives for site specific chemical delivery of commonly used NSAIDs to the inflamed tissues to minimize their GIT side effect or other systemic toxicities.
Yadav
Mange Ram
MR
Pharmacy Department, Faculty of Technology & Engineering, Kalabhavan, The M.S. University of Baroda, Vadodara 390001, India. mryadav11@yahoo.co.in
Pawar
Vijay P
VP
Marvaniya
Sejal M
SM
Halen
Parmeshwari K
PK
Giridhar
Rajani
R
Mishra
Anil K
AK
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism; D002351:Carrageenan / Q000008:administration & dosage; D004487:Edema / Q000000981:diagnostic imaging / Q000188:drug therapy; D004952:Esters / Q000737:chemistry*; D015902:Gamma Cameras; D006801:Humans; D007249:Inflammation / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D007719:Knee Joint / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D015609:Organotechnetium Compounds; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004952:Esters; D015609:Organotechnetium Compounds; D002351:Carrageenan