Dithiocarbamate chitosan as a potential polymeric matrix for controlled drug release

Abstract

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.

• Chitosan
• controlled release
• dithiocarbamate chitosan
• polymeric matrix
• tetracycline