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, Tmax and Cmax 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.