Effect of hyaluronic acid nanogels on the drugdelivery of cyclosporine administered subcutaneously in rats

Hyaluronic acid (HA) nanogel is derived by the partial modification of hyaluronicacid with cholesterol, causing the formation of self-assembled nanometer-scalehydrogel in water. Thus, HA nanogels might contribute to alter drug delivery ofpoorly water-soluble drugs. In this study, we tried to investigate the effect ofHA nanogels by using cyclosporine (CyA) in rats. HA nanogels (Asahi Kasei Co, 5mL/kg) containing CyA (2.5-15 mg/kg) were subcutaneously administered in male SDrats (Charles River) and whole blood samples were collected at the designatedtime-points up to 28 days. The concentrations of CyA were measured usingLC-MS/MS 6045 (Shimadzu). In rats administered CyA without HA nanogel (controlgroup), the concentration of CyA was below the detection limit (3 ng/mL) on 7days after administration. Some formulas of HA nanogel showed thesustained-release properties of CyA. Interestingly, one formula could bedetectable up to at least 10 days after administration. HA nanogels would beuseful as a tool to alter drug delivery of poorly water-soluble drugs such asCyA.