Oral Delivery of Pingyangmycin by Layer-by-Layer (LbL) Self-Assembly Polyelectrolyte-Grafted Nano Graphene Oxide

With the increasing development in scientific technology, building a nanocarrier system for cancer drugs has become a bliss for cancer patients. To allow for the oral administration of hydrophilic drugs, a nanocarrier that was based on negatively charged graphene oxide (GO) and prepared through the Layer-by-Layer (LbL) self-assembly of poly(acrylic acid)-cysteine (PAA-cys) and poly(allylamine hydrochloride) (PAH) was established. In the present study, we demonstrated the excellent biological properties of GO, the biological adhesiveness of PAA-cys, and the protection and controlled release profiles of polyelectrolyte. Pingyangmycin (PYM) was loaded onto the nanocarrier through non-covalent interactions. In vitro drug release studies of the prepared PAA-cys-PAH-GO-PYM were pH-sensitive and showed sustained release effects for over 8 h, before they were completely expelled by gastrointestinal peristalsis. Furthermore, cell viability experiments using A549 lung adenocarcinoma cells revealed that the IC50 of PAA-cys-PAH-GO-PYM, free drug, and GO-PYM were 159.241 μM, 134.960 μM, and 129.815 μM respectively, indicating the higher retention and cytotoxicity of PYM in vitro. When comparing the oral bioavailability of PYM with free drug, in vivo pharmacokinetics studies showed a 1.03-fold and 1.74-fold increase after GO loading and double-layer polyelectrolyte coating, respectively. Thus, PAA-cys-PAH-GO was successfully developed for oral delivery of PYM as anti-cancer therapy, and may provide further insight for oral administration of GO-based nanomaterials.