title: Development of cyclosporin A-loaded hyaluronic microsphere with enhanced oral bioavailability.
abstract: To develop a hyaluronic microsphere with the improved oral bioavailability of poorly water-soluble cyclosporin A (CsA), the microspheres were prepared with varying ratios of sodium hyaluronate (HA)/sodium lauryl sulfate (SLS)/CsA using a spray-drying technique. The effects of HA and SLS on the dissolution and solubility of CsA in microspheres were investigated. The CsA-microsphere prepared with HA/SLS/CsA at the ratio of 4/2/1 gave the highest solubility and dissolution rate of CsA among those formulae tested. As solubility and dissolution rate of CsA were increased about 17- and 2-fold compared to CsA powder, respectively, this CsA-microsphere was selected as an optimal formula for oral delivery in rats. The CsA-microsphere and Sandimmun neoral sol gave significantly higher blood levels compared with CsA powder alone. Moreover, the AUC, T(max) and C(max) values of CsA in CsA-microsphere were not significantly different from those in Sandimmun neoral sol in rats, indicating that CsA-microsphere was bioequivalent to the commercial product in rats. Our results demonstrated that the CsA-microsphere prepared with HA and SLS, with improved bioavailability of CsA, might have been useful to deliver a poorly water-soluble CsA.
authors.affiliation: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan 712-749, South Korea.
authors.forename: Jong Soo
authors.initials: JS
authors.lastname: Woo
authors.forename: Ming Guan
authors.initials: MG
authors.lastname: Piao
authors.forename: Dong Xun
authors.initials: DX
authors.lastname: Li
authors.forename: Dong-Sung
authors.initials: DS
authors.lastname: Ryu
authors.forename: Jun Young
authors.initials: JY
authors.lastname: Choi
authors.forename: Jung-Ae
authors.initials: JA
authors.lastname: Kim
authors.forename: Jeong Hoon
authors.initials: JH
authors.lastname: Kim
authors.forename: Sung Giu
authors.initials: SG
authors.lastname: Jin
authors.forename: Dae-Duk
authors.initials: DD
authors.lastname: Kim
authors.forename: Won Seok
authors.initials: WS
authors.lastname: Lyoo
authors.forename: Chul Soon
authors.initials: CS
authors.lastname: Yong
authors.forename: Han-Gon
authors.initials: HG
authors.lastname: Choi
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D016572:Cyclosporine / Q000008:administration & dosage* / Q000737:chemistry; D003627:Data Interpretation, Statistical; D004339:Drug Compounding; D016503:Drug Delivery Systems; D006820:Hyaluronic Acid / Q000737:chemistry*; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000737:chemistry; D007700:Kinetics; D008297:Male; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D006820:Hyaluronic Acid