Transdermal delivery of cyclosporin-A using electroporation. 1998

S Wang, and M Kara, and T R Krishnan
School of Pharmacy, Memorial University of Newfoundland, St. John's, Canada.

Topical delivery of cyclosporin A (CSA) is desirable for treating psoriasis, but it is hindered by the barrier property of stratum corneum, and the physicochemical properties of CSA. Attempts to deliver CSA from a solution prepared in 40% ethanol (EtOH) is phosphate buffered saline (PBS) using iontophoresis did not result in any significant increase in drug delivery, compared to passive. However, the use of electroporation pulses as a physical penetration enhancer enabled delivery of a significant amount of CSA. Single pulse electroporation study indicated that the amount of EtOH delivered across the skin increased as the applied electrode voltage (Uelectrode) was increased. However, it did not translate into a proportional increase in the delivery of CSA and only a three to four times increase, compared to passive delivery, was seen with the single purse electroporation. The drug contact duration had a varying effect in the efficiency of transdermal delivery of CSA. Four hour contact duration was chosen for the multiple pulse study. Use of multiple pulses (25 pulses, 10 ms each) at Uelectrode 200 V resulted in a sixty-fold increase, compared to passive, in the delivery of CSA to the skin. Transdermally delivered CSA was mostly bound to the skin and only a small amount was seen to cross the full skin into the receiver compartment. In a study of solvent transport, the flux of water was up to three times larger than that of EtOH after electroporation.

UI MeSH Term Description Entries
D007166 Immunosuppressive Agents Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging. Immunosuppressant,Immunosuppressive Agent,Immunosuppressants,Agent, Immunosuppressive,Agents, Immunosuppressive
D007478 Iontophoresis Therapeutic introduction of ions of soluble salts into tissues by means of electric current. In medical literature it is commonly used to indicate the process of increasing the penetration of drugs into surface tissues by the application of electric current. It has nothing to do with ION EXCHANGE; AIR IONIZATION nor PHONOPHORESIS, none of which requires current. Iontophoreses
D000279 Administration, Cutaneous The application of suitable drug dosage forms to the skin for either local or systemic effects. Cutaneous Drug Administration,Dermal Drug Administration,Drug Administration, Dermal,Percutaneous Administration,Skin Drug Administration,Transcutaneous Administration,Transdermal Administration,Administration, Dermal,Administration, Transcutaneous,Administration, Transdermal,Cutaneous Administration,Cutaneous Administration, Drug,Dermal Administration,Drug Administration, Cutaneous,Skin Administration, Drug,Administration, Cutaneous Drug,Administration, Dermal Drug,Administration, Percutaneous,Administrations, Cutaneous,Administrations, Cutaneous Drug,Administrations, Dermal,Administrations, Dermal Drug,Administrations, Percutaneous,Administrations, Transcutaneous,Administrations, Transdermal,Cutaneous Administrations,Cutaneous Administrations, Drug,Cutaneous Drug Administrations,Dermal Administrations,Dermal Drug Administrations,Drug Administrations, Cutaneous,Drug Administrations, Dermal,Drug Skin Administrations,Percutaneous Administrations,Skin Administrations, Drug,Skin Drug Administrations,Transcutaneous Administrations,Transdermal Administrations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012867 Skin The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.
D016503 Drug Delivery Systems Systems for the delivery of drugs to target sites of pharmacological actions. Technologies employed include those concerning drug preparation, route of administration, site targeting, metabolism, and toxicity. Drug Targeting,Delivery System, Drug,Delivery Systems, Drug,Drug Delivery System,Drug Targetings,System, Drug Delivery,Systems, Drug Delivery,Targeting, Drug,Targetings, Drug
D016572 Cyclosporine A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed). Cyclosporin A,Ciclosporin,CsA-Neoral,CyA-NOF,Cyclosporin,Cyclosporine A,Neoral,OL 27-400,Sandimmun,Sandimmun Neoral,Sandimmune,CsA Neoral,CsANeoral,CyA NOF,OL 27 400,OL 27400
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D018274 Electroporation A technique in which electric pulses, in kilovolts per centimeter and of microsecond-to-millisecond duration, cause a loss of the semipermeability of CELL MEMBRANES, thus leading to ion leakage, escape of metabolites, and increased uptake by cells of drugs, molecular probes, and DNA. Depending on the dosage, the formation of openings in the cell membranes caused by the electric pulses may or may not be reversible. Electric Field-Mediated Cell Permeabilization,Irreversible Electroporation,Reversible Electroporation,Electropermeabilisation,Electric Field Mediated Cell Permeabilization,Electroporation, Irreversible,Electroporation, Reversible

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