Novel microemulsion in situ electrolyte-triggered gelling system for ophthalmic delivery of lipophilic cyclosporine A: in vitro and in vivo results.
The objective of the present study was to design a novel microemulsion in situ electrolyte-triggered gelling system for ophthalmic delivery of a lipophilic drug, cyclosporine A (CsA). A CsA-loaded microemulsion was prepared using castor oil, Solutol HS 15 (surfactant), glycerol and water. This microemulsion was then dispersed in a Kelcogel solution to form the final microemulsion in situ electrolyte-triggered gelling system. In vitro, the viscosity of the CsA microemulsion Kelcogel system increased dramatically on dilution with artificial tear fluid and exhibited pseudo-plastic rheology. In vivo results revealed that the AUC(0-->32 h) of corneal CsA for the microemulsion Kelcogel system was approximately three-fold greater than for a CsA emulsion. Moreover, at 32 h after administration, CsA concentrations delivered by the microemulsion Kelcogel system remained at therapeutic levels in the cornea. This CsA microemulsion in situ electrolyte-triggered gelling system might provide an alternative approach to deliver prolonged precorneal residence time of CsA for preventing cornea allograft rejection.
Gan
Li
L
School of Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
Gan
Yong
Y
Zhu
Chunliu
C
Zhang
Xinxin
X
Zhu
Jiabi
J
D000818:Animals; D019540:Area Under Curve; D002368:Castor Oil / Q000737:chemistry; D003315:Cornea / Q000378:metabolism; D016572:Cyclosporine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004573:Electrolytes / Q000737:chemistry*; D004655:Emulsions; D005079:Excipients / Q000737:chemistry*; D005782:Gels; D005990:Glycerol / Q000737:chemistry; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D009883:Ophthalmic Solutions; D011092:Polyethylene Glycols / Q000737:chemistry; D011817:Rabbits; D012212:Rheology; D013229:Stearic Acids / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry; D014783:Viscosity; D014867:Water / Q000737:chemistry
D004573:Electrolytes; D004655:Emulsions; D005079:Excipients; D005782:Gels; D007166:Immunosuppressive Agents; D009883:Ophthalmic Solutions; D013229:Stearic Acids; D013501:Surface-Active Agents; D014867:Water; D011092:Polyethylene Glycols; C067028:Solutol HS 15; D002368:Castor Oil; D016572:Cyclosporine; D005990:Glycerol