Modification of cyclosporin A and conjugation of its derivative to HPMA copolymers

Cyclosporin A (CsA) was epoxidized with m-chloroperoxybenzoic acid in the p resence of sodium carbonate or with tert-butyl hydroperoxide in the presenc e of dioxomolybdenum iminodiethanoxide. The CsA epoxide was not stable and rearranged into a compound with a more stable five-member ring structure. A n amino group containing cyclosporin A derivative (CsA amine) was obtained by the reaction of CsA epoxide with excess ethylenediamine. The yield of th e CsA amine was 30-40% based on the CsA. An HPMA copolymer-CsA conjugate wa s prepared by the reaction of the CsA amine with an HPMA and MA-Gly-Phe-Leu -Gly-ONp copolymer. The content of CsA amine in the conjugate was 8.7 wt%. The CsA amine was released from the copolymer by enzymatic hydrolysis with papain.