Development of cyclosporin A-loaded hyaluronic microsphere with enhanced oral bioavailability.
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.
Woo
Jong Soo
JS
College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan 712-749, South Korea.
Piao
Ming Guan
MG
Li
Dong Xun
DX
Ryu
Dong-Sung
DS
Choi
Jun Young
JY
Kim
Jung-Ae
JA
Kim
Jeong Hoon
JH
Jin
Sung Giu
SG
Kim
Dae-Duk
DD
Lyoo
Won Seok
WS
Yong
Chul Soon
CS
Choi
Han-Gon
HG
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
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D006820:Hyaluronic Acid