Objective: To develop a polymer matrix for controlled release of drugs, chitosan, a linear aminopolysaccharide, was chemically modified to dithiocarbamate chitosan (DTCC) to afford a matrix where metal-drug complexes could be attached and released in a controlled manner depending on the binding nature between the drugs and the metals.
Materials and methods: DTCC was treated with metal-tetracycline (Tc) complexes to prepare DTCC-Ca(II)-Tc, DTCC-Mg(II)-Tc, DTCC-Cu(II)-Tc and DTCC-Zn(II)-Tc.
Results: The binding amount of Tc was in the order of DTCC-Zn(II)-Tc ≈ DTCC-Mg(II)-Tc ≈ DTCC-Ca(II)-Tc > DTCC-Cu(II)-Tc. The biphasic binding profiles, where Tc binding increased initially and then decreased, were shown for DTCC-Cu(II)-Tc and DTCC-Zn(II)-Tc. In a flow method, Tc was released slowly from DTCC-metal-Tc complexes except for DTCC-Cu(II)-Tc compared with Tc release from DTCC-Tc. In parallel with the results of the release experiment, DTCC-metal-Tc complexes except for DTCC-Cu(II)-Tc presented a prolonged antibacterial activity in an antibacterial test. The antibacterial activity of DTCC-Ca(II)-, -Mg(II)- and -Zn(II)-Tc complexes lasted for 28-44 days, while free Tc and DTCC-Tc lasted for 7-12 days.
Discussion and conclusion: Taken together, our data suggest that DTCC could be used for a polymeric matrix for controlled release of drugs such as Tc, which possess functional groups for ionic and/or coordinate bond with metals.