Electroporation and transcutaneous extraction of drugs

Summary

Principal Investigator: SATHYANARAYANA N MURTHY
Abstract: [unreadable] DESCRIPTION (provided by applicant): The time course of unbound drug in the the extracellular fluid (ECF) is critical in predicting the efficacy and toxicity of drugs such as antibiotics, anticancerous, antivirals etc. Unfortunately, the currently practiced methods of sampling drugs from the interstitial compartment are invasive and tedious. We propose to develop a noninvasive, simple and rapid "Electroporation and Transcutaneous extraction (ETE)" to sample the drugs from the dermal ECF. ETE is a method of reversibe permeabilization of skin by the application of short electrical pulses and sampling of drugs from dermal ECF. The research proposed in this application emanates from our recent success in utilizing ETE for sampling of drugs such as salicylic acid, acyclovir, ibuprofen, fluconazole and cefpodoxime from the dermal ECF. We found that the time course of unbound drug concentration in the dermal ECF determined by ETE is in agreement with that determined by dermal microdialysis. The ibuprofen levels in the dermal ECF correlated well with that in the synovial fluid. Similarly the concentration of unbound cefpodoxime in the dermal ECF correlated well with its concentration in the lung tissue. These results demonstrate the feasibility of this project. It also supports our objective that successful development of ETE will not only be signficant from the perspective of treating skin disorders, but also could serve as a surrogate for the drug levels in the rarely accessible tissues. The hypothesis of this proposal is that the transcutaneous extraction flux of drugs is proportional to the concentration of unbound drug in the dermal ECF. Knowing the reciprocal of permeability coefficient (1/P in vivo) of the skin, the unbound drug concentration in the dermal ECF could be determined. We propose three aims for the successful development of ETE as a noninvasive drug sampling technique. In Aim1, we will study the time course of unbound concentration of cephalexin, ciprofloxacin, 8-methoxypsoralen and penciclovir in the dermal ECF by ETE in hairless rat model. In Aim 2, we will assess the validity of ETE technique by comparing the time course of drugs in dermal ECF, determined by ETE with that determined by dermal microdialysis. In Aim 3, we plan to correlate the time course of unbound cephalexin and ciprofloxacin with their kinetics in the lung tissue (determined by microdialysis). Further we also plan to correlate the time course of unbound ciprofloxacin in dermal ECF with that in synovial fluid determined by microdialysis in rat. [unreadable] [unreadable] [unreadable]
Funding Period: 2006-09-01 - 2010-08-31
more information: NIH RePORT

Top Publications

  1. pmc Electroporation and transcutaneous sampling (ETS) of acyclovir
    S Narasimha Murthy
    J Dermatol Sci 49:249-51. 2008
  2. pmc Noninvasive transcutaneous sampling of glucose by electroporation
    S Srinivasa Murthy
    Department of Pharmaceutics, School of Pharmacy, The University of Mississippi, University, Mississippi
    J Diabetes Sci Technol 2:250-4. 2008
  3. pmc Transcutaneous sampling of ciprofloxacin and 8-methoxypsoralen by electroporation (ETS technique)
    Srinivasa M Sammeta
    Department of Pharmaceutics, The University of Mississippi, University, MS 38677, USA
    Int J Pharm 369:24-9. 2009
  4. pmc Dermal drug levels of antibiotic (cephalexin) determined by electroporation and transcutaneous sampling (ETS) technique
    S M Sammeta
    Department of Pharmaceutics, The University of Mississippi, University Mississippi 38677, USA
    J Pharm Sci 98:2677-85. 2009
  5. ncbi Transdermal drug delivery enhanced by low voltage electropulsation (LVE)
    S M Sammeta
    Department of Pharmaceutics, The University of Mississippi, University, MS 38677, USA
    Pharm Dev Technol 14:159-64. 2009

Detail Information

Publications5

  1. pmc Electroporation and transcutaneous sampling (ETS) of acyclovir
    S Narasimha Murthy
    J Dermatol Sci 49:249-51. 2008
  2. pmc Noninvasive transcutaneous sampling of glucose by electroporation
    S Srinivasa Murthy
    Department of Pharmaceutics, School of Pharmacy, The University of Mississippi, University, Mississippi
    J Diabetes Sci Technol 2:250-4. 2008
    ..The objective of this study was to investigate the efficiency of the noninvasive electroporation and transcutaneous sampling (ETS) technique for predicting blood glucose levels...
  3. pmc Transcutaneous sampling of ciprofloxacin and 8-methoxypsoralen by electroporation (ETS technique)
    Srinivasa M Sammeta
    Department of Pharmaceutics, The University of Mississippi, University, MS 38677, USA
    Int J Pharm 369:24-9. 2009
    ..The results show that ETS can be utilized as a potential technique for sampling of drugs from the dermal ECF...
  4. pmc Dermal drug levels of antibiotic (cephalexin) determined by electroporation and transcutaneous sampling (ETS) technique
    S M Sammeta
    Department of Pharmaceutics, The University of Mississippi, University Mississippi 38677, USA
    J Pharm Sci 98:2677-85. 2009
    ..9) between synovial fluid and dermal ECF levels of cephalexin indicating that dermal ECF levels could be used as a potential surrogate for cephalexin concentration in the synovial fluid...
  5. ncbi Transdermal drug delivery enhanced by low voltage electropulsation (LVE)
    S M Sammeta
    Department of Pharmaceutics, The University of Mississippi, University, MS 38677, USA
    Pharm Dev Technol 14:159-64. 2009
    ..It is evident from the results of this experiment that the transdermal delivery of drugs could be enhanced by LVE which is a rather mild technique than electroporation or iontophoresis...