New doxorubicin nanocarriers based on cyclodextrins

Polymeric nanoparticles and fibrin gels (FBGs) are attractive biomaterials for local delivery of a variety of biotherapeutic agents, from drugs to proteins. We combined these different drug delivery approaches by preparing nanoparticle-loaded FBGs characterized by their intrinsic features of drug delivery rate and antiproliferative/apoptotic activities. Inclusion complexes of doxorubicin (DOXO) with oligomeric beta-cyclodextrins (oCyD) functionalized with different functional groups were studied. These nanocarriers were able to interact with FBGs as shown by a decreased release rate of DOXO. One of these complexes, oCyDNH(2)/DOXO, demonstrated good antiproliferative and apoptotic activity in vitro, reflecting a higher drug uptake by cells. As hypothesized, the nanocarrier/FBG complexes showed a lower drug release rate than similar FBGs loaded with the corresponding non-functionalized oCyD/DOXO. Taken together, our results provide experimental evidence that oCyDNH(2)/DOXO complexes may be useful components in enhanced FBGs and further build support for the great promise these complex molecules hold for clinical use in localized anticancer therapy of inoperable or surgically removable tumors of different histological origin.