Desferrioxamine mesylate encapsulated novel chitosan based polymeric nanocomposites: insights into drug interaction, biocompatibility, cytotoxicity, cell permeability, antioxidant and controlled release properties.

Desferrioxamine (DFO) is a clinically established iron chelator used to manage iron overload in transfusion-dependent thalassemia patients. Despite its efficacy, DFO's poor cellular permeability and burst release profile limit its application to subcutaneous administration, precluding its use as an oral formulation. To address these limitations, DFO was encapsulated in a nanocomposite matrix composed of chitosan (CTS), polyethylene oxide (PEO), ethyl cellulose (EC), and tripolyphosphate (TPP). The resulting nanocomposites were comprehensively characterized using scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), particle size analysis (PSA), and Fourier-transform infrared spectroscopy (FT-IR). The evaluation assessed drug release behavior at physiological pH, intestinal pH, and cellular uptake in HeLa cell lines. Among the tested formulations, DFO_PEO_EC_CTS_TPP_1 exhibited the highest drug loading capacity (285.56 ± 0.04 mg g), entrapment efficiency (85.67 ± 13.35%), and antioxidant activity. Drug release kinetics were best described by the Peppas-Sahlin model ( = 0.9999), indicating a Case II relaxation-controlled mechanism, supporting a sustained release profile. Blood compatibility was confirmed through Wilks' Lambda test, comparing coagulation parameters (APTT, PT) and complement levels (C3) between control and treated samples, including Fe(iii)-DFO_PEO_EC_CTS_TPP_1 at 0.5 mg mL and 37 °C. No statistically significant differences were observed (, PT, = 0.052), confirming the hemocompatibility of the formulation. The MTT cytotoxicity assay for the optimal formulation yielded an IC value of 29.9 ± 5 μM, indicating acceptable cytocompatibility. Furthermore, the formulation demonstrated enhanced DFO permeability across cell membranes and sustained drug release over time. In conclusion, encapsulation of DFO within the PEO_EC_CTS_TPP nanocomposite matrix presents a promising strategy to overcome the limitations of native DFO, offering improved cell permeability, biocompatibility, and controlled release, potentially advancing it toward more effective therapeutic applications.