Gelatin-stabilised microemulsion-based organogels facilitates percutaneous penetration of Cyclosporin A in vitro and dermal pharmacokinetics in vivo.
Gelatin-stabilised microemulsion-based organogels (MBGs) are very useful in transdermal and topical delivery of hydrophobic drugs because of their lipophilic nature. MBGs systems possessing a potentially improved skin bioavailability of Cyclosporin A were designed and explored for some characteristics. The release characteristics of drug from MBGs were studied according to drug concentration. As the concentration of drug increased, the release of drug from gel increased, showing concentration dependency. Percutaneous penetration studies using rat skin in vitro showed that the deposition of Cyclosporin A was significantly improved by MBGs compared to the control. We also evaluated the therapeutic advantage of dermal administration of Cyclosporin A 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 MBGs containing Cyclosporin A, the deposition of the drug into skin and subcutaneous fat was, respectively, almost 55- and 3-fold higher than the concentrations compared with oral administration. Systemic distribution in blood, liver and kidney was much lower following topical than following oral administration. With high local concentrations and minimal distribution to other organs via the circulation, topical applied MBGs loaded with Cyclosporin A might deliver maximal therapeutic effect to local tissue while avoiding the side effects seen with systemic therapy. The histopathological findings revealed that the new MBGs vehicle was a safe vehicle for topical drug delivery systems.
Liu
Hongzhuo
H
School of Pharmacy, Pharmaceutical University of Shenyang, Shenyang 110016, People's Republic of China.
Wang
Yongjun
Y
Han
Fei
F
Yao
Huimin
H
Li
Sanming
S
D000279:Administration, Cutaneous; D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D004553:Electric Conductivity; D004655:Emulsions; D005780:Gelatin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D005782:Gels / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012869:Skin Absorption; D014018:Tissue Distribution
D004655:Emulsions; D005782:Gels; D016572:Cyclosporine; D005780:Gelatin