Chemically Cross-Linked Hybrid Nanogels of Alginate and PAMAM Dendrimers as Efficient Anticancer Drug Delivery Vehicles

Proper choice and design of nanocarriers is imperative to achieve the desired therapeutic benefits. Herein, we report a facile methodology for preparation of chemically cross-linked AG-GS hybrid nanogels of alginate (AG) and G5.0 poly(amidoamine) (PAMAM) dendrimer via carbodiimide chemistry. The rationale behind the formulation of AG-GS nanogels is to attain effective and sustained delivery of chemotherapeutic agents. Physical entrapment of anticancer drug epirubicin (EPI) within AG-G5 nanogels endows them with therapeutic properties. Analytical techniques such as zeta potential (zeta) measurements, field-emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), and Fourier transform infrared spectroscopy (FTIR) confirm the integration of PAMAM dendrimer with alginate structure. Thermal, swelling studies, and surface area estimations suggest improved stability and porosity of AG-GS nanogels. Moreover, AG-GS nanogels exhibited significantly better mechanical properties and pH dependent release of EPI than AG nanogels. Fluorescence microscopy, cell viability assay, cell cycle analysis and FE-SEM imaging indicated apoptosis inducing potential of EPICAG-GS nanogels by enhanced intracellular EPI accumulation in breast cancer (MCF-7) cells. Overall, our results put forth AG-G5 hybrid nanogels as prospective candidates to achieve enhanced anticancer effects in vitro.