Bicontinuous Cyclosporin a Loaded Water-AOT/Tween 85-Isopropylmyristate Microemulsion: Structural Characterization and Dermal Pharmacokinetics In Vivo

Topical delivery of Cyclosporin A (CysA) is of great interest for the treatment of autoimmune skin disorders. Microemulsion systems prepared by AOT/Tween85/isopropyl myristate (IPM)/water possessing a potentially improved skin bioavailability of CysA were designed. The structure of microemulsions wa...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 2009-03, Vol.98 (3), p.1167-1176
Main Authors: Liu, Hongzhuo, Wang, Yongjun, Lang, Yiyong, Yao, Huimin, Dong, Yang, Li, Sanming
Format: Article
Language:English
Subjects:
Administration, Oral
Administration, Topical
Aerosols - chemistry
Animals
Biological and medical sciences
Calorimetry, Differential Scanning
Cyclosporin A
Cyclosporine - administration & dosage
Cyclosporine - pharmacokinetics
Cyclosporine - toxicity
DOSY
Drug Delivery Systems
DSC
Emulsions - administration & dosage
Emulsions - chemistry
Emulsions - pharmacokinetics
Emulsions - toxicity
General pharmacology
in vivo
Magnetic Resonance Spectroscopy
Male
Medical sciences
microemulsion
Myristates - chemistry
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Polysorbates - chemistry
Rats
Rats, Sprague-Dawley
skin
Skin - metabolism
Skin - pathology
topical delivery
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Summary:Topical delivery of Cyclosporin A (CysA) is of great interest for the treatment of autoimmune skin disorders. Microemulsion systems prepared by AOT/Tween85/isopropyl myristate (IPM)/water possessing a potentially improved skin bioavailability of CysA were designed. The structure of microemulsions was investigated by diffusion-ordered NMR spectroscopy (DOSY) and differential scanning calorimetry (DSC) measurements. The DOSY measurements indicated the presence of bicontinuous and water-in-oil microemulsions depending on microemulsion composition. The DSC measurement confirmed that the microemulsion containing 30.0wt% water was bicontinuous type, in agreement with the DOSY findings. We also evaluated the therapeutic advantage of dermal administration of CysA in rat model. Local (subcutaneous and skin), systemic concentrations and organ distribution (liver and kidney) were evaluated serially following topical and oral application of the drug. In rat dermal applied with the bicontinuous microemulsion containing CysA, the deposition of the drug into skin and subcutaneous fat was respectively almost 30 and 15-fold higher than the concentrations compared with oral administration. Systemic distribution in blood, liver and kidney was much lower following topical administration than that of following oral administration. With high local concentrations and minimal distribution to other organs via the circulation, topical microemulsion vehicle loaded with CysA might deliver maximal therapeutic effect to local tissue while avoiding side effects seen with systemic therapy. The histopathological findings revealed that the new bicontinuous microemulsion was a safe vehicle for topical drug delivery of CysA.
ISSN:0022-3549
1520-6017
DOI:10.1002/jps.21485