Desferrioxamine release from gelatin-based systems

Abstract

The conventional treatment with regular red-blood-cell transfusions and simultaneous chelation of excess iron with DFO (desferrioxamine) improves quality of life of thalassaemic patients while increasing their rate of survival considerably. Although DFO is the main iron-chelating drug currently utilized, it has various drawbacks, including high cost, poor oral effectiveness, toxicity and short plasma half-life. it has to be administered by slow, subcutaneous infusion during blood transfusion for 8-12 h at night, 5-7 nights a week, and this leads to a very poor patient compliance. In order to avoid frequent and uncomfortable infusions of DFO, application of controlled-release systems might be alternative routes in the supportive treatment of thalassaemia. In the present study, GMs (gelatin microspheres) and GFs (gelatin films) were prepared by coacervation and casting methods respectively to develop controlled DFO-release systems. Cross-linking by glutar aldehyde and carbodi-imide were performed to increase the stability of gelatin matrices. Microspheres and films prepared without the addition of crosslinker degraded completely in 4 h. On the other hand, addition of cross-linker extended this time from hours to weeks depending on the added amount. Therefore the amount of DFO released from microspheres in 7 days was found to be in the range 12-82%, whereas the amount permeated through the films in 5.0 h was found to be in the range 34-67%. GFs were elastic and demonstrated good mechanical properties. Films achieved 0.14-0.69 MPa tensile strength, with 0.12-1.29 MPa elastic modulus and 26.49-109.38% strain values at break point. These studies showed that gelatin-based controlled-release systems could be improved and could be good candidates for the production of long-term DFO-carrying systems.