Stearyl polyoxyethylene-grafted heparin nanogel for oral delivery of Cisplatin: enhanced drug loading capacity and anticancer efficacy

In this work, novel nanoparticles based on stearyl polyoxyethylene ether (Brij S100) and heparin for oral delivery of cisplatin were developed. The Brij S100 was covalently grafted with heparin (Hep) via the help of cystamine as a linker molecule and the successful conjugation of Hep and Brij S100 was proved by FT-IR and ¹H-NMR spectroscopy techniques. The Hep-Brij S100 copolymer was self-assembled to form the micelle structure at the minimum concentration (CMC value) of 392 ± 23 µg/ml. Cisplatin (Cis) was loaded into the Hep-Brij S100 nanogels with high drug loading content (4.88%) and efficiency (93.60%). The results of DLS and SEM revealed the nanoscale of particles (170.5 nm) with homogeneity of dispersed colloidal nanoparticles. The in vitro release of Cis from Hep-Brij S100 nanogel followed the Fickian diffusion. Furthermore, the pH-responsive release profile of Cis showed that Hep-Brij S100 nanoformulation was suitable for oral administration, without inducing any cytotoxic effect on normal cells, even at the high concentration (100 mg/ml). Importantly, the Hep-Brij S100/Cis nanomedicine exerted better cytotoxicity (IC₅₀ = 3.26 ± 0.19 µg/mL) than that of the free Cis (52.81 ± 6.26 µg/mL) on MCF7-breast cancer cells. These results strongly indicated that Hep-Brij S100 nanogels possess great potential for the oral delivery of chemotherapies.