Development and Characterization of Carboxymethyl Assam Bora Rice Starch-Coated Superparamagnetic Iron Oxide Nanoparticles (CM-ABRS SPIONs) for Magnetically Guided Targeted Delivery of Doxorubicin in Cancer Therapy

Abstract

The present study reports the synthesis, physicochemical characterization, and biological evaluation of doxorubicin (DOX)-loaded carboxymethyl Assam Bora rice starch-coated superparamagnetic iron oxide nanoparticles (DOX–CM-ABRS SPIONs) as a novel magnetically guided targeted drug delivery system for cancer therapy. Native Assam Bora rice starch (ABRS) was chemically modified by carboxymethylation using monochloroacetic acid under alkaline conditions in isopropyl alcohol, yielding CM-ABRS with an optimized degree of substitution (DS) of 1.23. The modified polymer was comprehensively characterized by FT-IR, ¹H/¹³C NMR, CHN analysis, XRD, DSC, SEM, rheology, swelling index, and mucoadhesive studies, confirming successful introduction of carboxymethyl groups and significant improvement in physicochemical properties — including a ~60-fold enhancement in aqueous solubility compared to native starch. CM-ABRS was subsequently employed as a hydrophilic coating agent for the preparation of SPIONs by co-precipitation. DOX was loaded onto CM-ABRS SPIONs via electrostatic interaction between the positively charged amine group of DOX and the negatively charged carboxylate moieties of CM-ABRS, achieving a drug loading of ~6% (w/w) and entrapment efficiency of 90.24 ± 0.8%. The optimized formulation (dc-7) exhibited a mean particle size of ~205 nm (PDI 0.38) with zeta potential of −26.0 mV, spherical morphology by TEM, and confirmed superparamagnetic behavior (saturation magnetization ~33.5 emu/g) by VSM. In vitro drug release in phosphate-buffered saline (pH 7.4) demonstrated a controlled sustained-release profile (~68.2% in 24 h) best fitted to the Higuchi model (R² = 0.937). In vitro magnetic targeting studies in a glass microcapillary confirmed the proof-of-concept for magnetically guided delivery. Cytotoxicity evaluation against MCF-7 breast cancer cells revealed a markedly lower IC₅₀ (~5.95 µg/mL) for DOX–CM-ABRS SPIONs compared to conventional DOX solution (~12.16 µg/mL) (p < 0.05). Molecular docking against the HER-2 receptor (PDB: 5JEB) demonstrated a more favorable docking score (−13.396) for the DOX–SPION formulation versus free DOX (−12.537). These findings establish CM-ABRS SPIONs as a promising, green, biodegradable, and cost-effective nanoplatform for targeted anticancer drug delivery.