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

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Abstract

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.

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Authors and Affiliations

  1. Department of Pharmaceutics, School of Pharmacy, The University of Mississippi, 113 Faser Hall, University, Mississippi, 38677, USA

    Srinivasa M. Sammeta & S. Narasimha Murthy

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  1. Srinivasa M. Sammeta
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  2. S. Narasimha Murthy
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Correspondence to S. Narasimha Murthy.

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Sammeta, S.M., Murthy, S.N. “ChilDrive”: A Technique of Combining Regional Cutaneous Hypothermia with Iontophoresis for the Delivery of Drugs to Synovial Fluid. Pharm Res 26, 2535–2540 (2009). https://doi.org/10.1007/s11095-009-9977-0

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  • DOI: https://doi.org/10.1007/s11095-009-9977-0

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