RGD-modified solid lipid nanoparticles improve oral doxorubicin absorption: In vitro and in vivo study

Abstract

ObjectiveDoxorubicin (DOX), an effective antitumor drug, is widely used in cancer treatment. However, DOX has low oral bioavailability. Owing to its ability to specifically bind the β1 receptor on the surface of M cells, promote the phagocytosis of drugs by M cells, and improve the oral efficacy of drugs, arginine-glycine-aspartic peptide (RGD) is used to modify the oral nanodrug delivery system. MethodsAn emulsion solvent evaporation method was used to prepare DOX-loaded solid lipid nanoparticles (DOX-SLNs), which were further modified with RGD (RGD-DOX-SLNs) by noncovalent interactions. The physicochemical properties, dissolution rate, and cytotoxicity of the SLNs were investigated. An in vitro transparency experiment was performed using the follicle-associated epithelium (FAE) model. In addition, oral bioavailability and gastrointestinal (GI) mucosal irritation were evaluated in rats. ResultsThe cumulative release percentage of DOX at pH 1.2 decreased significantly when DOX was incorporated into the SLNs, which may be dependent on drug diffusion and matrix erosion mechanisms. The cell toxicity was low in Caco-2 cells. No GI mucosal irritation was found in rats. The cellular uptake of RGD-DOX-SLNs in the FAE model was higher than in Caco-2 model. Compared with the DOX group, the area under the plasma concentration-time curve (AUC) of DOX in the RGD-DOX-SLNs group increased 2.25-fold after oral administration to rats. ConclusionsRGD-DOX-SLNs improved DOX transport in the FAE model and enhanced the oral bioavailability of DOX in rats.