Nanoalginates via Inverse-Micelle Synthesis: Doxorubicin-Encapsulation and Breast Cancer Cytotoxicity

Abstract Crosslinked-biopolymer nanoparticles provide a convenient platform for therapeutic encapsulation and delivery. Here, we present a robust inverse-micelle process to load water-soluble drugs into a calcium-crosslinked alginate matrix. The utility of the resulting nanoalginate (NALG) carriers was assessed by a doxorubicin (DOX) formulation (NALG-DOX) and evaluating its potency on breast cancer cells (4T1). This facile synthesis process produced doxorubicin-containing particles of ~ 83 nm by hydrodynamic size and zeta potential ~ 7.2 mV. The cyclohexane/dodecylamine microemulsion yielded uniform and spherical nanoparticles as observed by electron microscopy. The uptake of the drug from the NALG-DOX formulation in 4T1 cells was observed by fluorescence microscopy employing doxorubicin’s inherent fluorescence. Therapeutic efficacy of the NALG-DOX against 4T1 cells was demonstrated qualitatively through a LIVE/DEAD fluorescence assay and quantitatively via cell viability assay (Alamar Blue). In addition, IC50 values were determined, with encapsulated doxorubicin having a slightly higher value. No toxicity of the empty NALG carrier was observed. Overall, these results demonstrate the utility of this synthesis process for encapsulation of hydrophilic therapeutics and NALG to function as a drug carrier.