“ChilDrive”: A Technique of Combining Regional Cutaneous Hypothermia with Iontophoresis for the Delivery of Drugs to Synovial Fluid

• Published in: Pharmaceutical research 2009-11, Vol.26 (11), p.2535-2540
• Main Authors: Sammeta, Srinivasa M, Murthy, S. Narasimha
• Format: Article
• Language: English
• Subjects: Administration, Cutaneous; Animals; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - pharmacokinetics; Arthritis; Biochemistry; Biological and medical sciences; Biological Availability; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Body fluids; Diclofenac - administration & dosage; Diclofenac - pharmacokinetics; Drug Delivery Systems; General pharmacology; Hypothermia, Induced; intraarticular microdialysis; Iontophoresis; Male; Medical Law; Medical sciences; Models, Biological; Pharmaceutical technology. Pharmaceutical industry; Pharmacology; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pharmacy; Prednisolone - administration & dosage; Prednisolone - pharmacokinetics; Rats; Rats, Sprague-Dawley; Research Paper; Rodents; synovial fluid; Synovial Fluid - chemistry; targeting; transdermal; Transdermal medication
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-009-9977-0

Purpose 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 AUC₀₋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 µg.h/ml for diclofenac sodium and prednisolone sodium phosphate, respectively). CD resulted in an AUC₀₋t of 5.2 ± 0.69 and 24.6 ± 1.97 µg.h/ml for diclofenac sodium and prednisolone sodium phosphate which was ~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.