Implantable slow release cyclosporin A (CYA) delivery system to thoracic lymph duct

An implant from which cyclosporin A (CyA) is slowly released has been prepared and the immunosuppressive effect of such a CyA implant was studied with an allogenic rat heart transplantation model system. The implant was made of a biodegradable polymer of L-lactic acid (PLA) and/or co-polymer of L-lactic acid and glycolic acid (PLGA) as the base. The synthetic nonionic surfactant, HCO-60 (polyoxyethylated, 60μmol, castor oil derivative), was used as an additive. By changing the contents of the polymer and HCO-60, the release rate of CyA was adjusted. To determine the kind and formulation of the base, the lipophilic dye, Sudan Black (SB), was used as a model drug for CyA. Implants made of PLGA and HCO-60 (10:15) released more than 45% of SB within 6 days, whereas PLA implants released less than 15%. Based on these results, an implant containing CyA from which 70 ± 9.7% of the formulated CyA was released within 6 days was prepared. The size of the implant was 2 mm (o.d.)× 15 mm length. The immunosuppressive activities of CyA administered as an implant attached to the thoracic duct were evaluated with an allogenic rat heart transplantation model system. As a control, a placebo implant was used. The CyA implant showed a cardiac graft survival period of 9.8 ± 1.3 (mean ±S.D.) and 21.0 ± 9.6 days at 20 and 35 mg/kg, respectively, which is significantly longer than that of the placebo implant rat group (7.6 ± 0.9 days). These results demonstrate the possibility of local immunosuppression at the thoracic lymph in immunosuppressive therapy with CyA.