Characterization of in-vitro drug release and biological activity of methotrexate-bovine serum albumin conjugates.

Two series of methotrexate (MTX)-bovine serum albumin (BSA) conjugates have been prepared containing either 96 +/- 16 mg (mean +/- s.d.) or 32 +/- 13 mg of MTX per gram of conjugate. The conjugates released MTX in-vitro in a biphasic manner, the release rate being dependent on the quantity of MTX in the conjugate and on the pH of the release medium. An initial rapid release over 6 h appears to be due to physically adsorbed MTX with the slower secondary release due to covalently bound drug. The conjugates retain a degree of antineoplastic activity in-vitro, but this might be related to the small fraction of MTX that is tightly physically bound.