Fe-bLf or
paclitaxel (Taxol®) were adsorbed onto
calcium phosphate nanocores, enclosed in biodegradable
polymers chitosan and
alginate. The Fe-bLf or
Taxol-loaded NCs indicated as AEC-CP-Fe-bLf or AEC-CP-
Taxol NCs, respectively, were made by combination of ionic gelation and nanoprecipitation. Size distribution, morphology, internalization and release profiles of the NCs were studied along with evaluation of in vitro and in vivo anticancer activities and compared with
paclitaxel.
RESULTS: AEC-CP-Fe-bLf NCs obtained spherical morphology and showed enhanced endocytosis, transcytosis and anticancer activity in Caco-2 cells in vitro. AEC-CP-Fe-bLf NCs were supplemented in an AIN 93G diet and fed to mice in both prevention and treatment human xenograft
colon cancer models. AEC-CP-Fe-bLf NCs were found to be highly significantly effective when given orally, as a pretreatment, 1 week before Caco-2 cell
injections. None of the mice from the AEC-CP-Fe-bLf NC-fed group developed
tumors or showed any signs of toxicity, while the mice fed the control AIN 93G diet showed normal
tumor growth. Fe-bLf or
Taxol, when given orally in a diet as nanoformulations post-
tumor development, showed a significant regression in the
tumor size with complete inhibition of
tumor growth later, while intratumoral injection of
Taxol just delayed the growth of
tumors. The pharmacokinetic and bioavailability studies indicated that nanoformulated Fe-bLf was predominantly present on
tumor cells compared to non-nanoformulated Fe-bLf. Fe-bLf-loaded NCs were found to help in absorption of
iron and thus may have utility in enhancing the
iron uptake during
iron deficiency without interfering with the absorption of
calcium.
CONCLUSION: With the promising results of our study, the future potential of NC-loaded Fe-bLf in
chemoprevention and in the treatment of human
colon cancer, deserves further investigation for translational research and preclinical studies of other
malignancies.