Macromolecular Co-conjugate of Ferrocene and Bisphosphonate: Synthesis, Characterization and Kinetic Drug Release Study

Abstract

Cancer chemotherapy often results in side effects such as high toxicity and drug resistance. Sequential and simultaneous delivery of drug combinations have been found to reduce the side effects associated with systemic delivery of anticancer drugs. An alternative approach to systemic delivery of anticancer drugs is the co-conjugation of two or more of these agents to a single polymeric carrier via biofissionable linkages. In this study, macromolecular co-conjugates of bisphosphonate and ferrocene were synthesized and the kinetic drug release studied. Phosphorus and proton NMR and FTIR were used to characterize the co-conjugates. The mass percentages incorporation of ferrocene analogue were found to be between 4–5 % and 10–12 % for bisphosphonate. Kinetic drug release results at selected pH (1.2, 5.5 and 7.4) were fitted in different mathematical drug release model to determine the mechanism of release of ferrocene and bisphosphonate from a co-conjugate pro-drug. The best model describing the release of ferrocene were found to be Korsmeyer–Peppas model at pH 1.2 and zero order model at pH 5.5 and 7.4. For bisphosphonate, Korsmeyer–Peppas, Higuchi and zero order models were found to best fit the release mechanism at pH 1.2, 5.5 and 7.4 respectively.