"ChilDrive": a technique of combining regional cutaneous hypothermia with iontophoresis for the delivery of drugs to synovial fluid.
OBJECTIVE
Bioavailability of drugs in the synovial fluid when administered via transdermal route is highly limited due to the dermal clearance. The purpose of this project was to assess the efficiency of ChilDrive (CD) technique to improve the drug targeting to the synovial fluid. CD is a technique of transdermal delivery of drugs combining regional hypothermia and iontophoresis.


METHODS
Diclofenac sodium and Prednisolone sodium phosphate were administered by transdermal route (Passive, Iontophoresis, Chil-Passive and ChilDrive) at the knee-joint region of hind limb in sprague dawley rats for 6 h. Intraarticular microdialysis was carried out to determine the time course of drug concentration in the synovial fluid. Drug levels in synovial fluid after intravenous and intraarticular administration were also determined.


RESULTS
Iontophoretic delivery increased the AUC(0-t) (area under the curve) of drugs in the synovial fluid by 3-fold over passive delivery (0.86 +/- 0.04 and 2.0 +/- 0.06 microg.h/ml for diclofenac sodium and prednisolone sodium phosphate, respectively). CD resulted in an AUC(0-t) of 5.2 +/- 0.69 and 24.6 +/- 1.97 microg.h/ml for diclofenac sodium and prednisolone sodium phosphate which was approximately 6-12-fold higher than the passive and 2-4-fold higher than iontophoresis.


CONCLUSIONS
The results support our hypothesis that CD improves bioavailability of drugs to the synovial joints. CD could be developed as a potential noninvasive technique for treatment of arthritis.
Department of Pharmaceutics, School of Pharmacy, The University of Mississippi, University, Mississippi 38677, USA.
Srinivasa M
SM
Sammeta
S Narasimha
SN
Murthy
D000279:Administration, Cutaneous; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001682:Biological Availability; D004008:Diclofenac / Q000008:administration & dosage / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D007036:Hypothermia, Induced; D007478:Iontophoresis; D008297:Male; D008954:Models, Biological; D011239:Prednisolone / Q000008:administration & dosage / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013582:Synovial Fluid / Q000737:chemistry*
D000893:Anti-Inflammatory Agents; D004008:Diclofenac; D011239:Prednisolone