Characterization and in vitro evaluation of melanin nanoparticles as an oral drug delivery system: Studies using Caco-2 cell model and molecular dynamics simulations

Abstract

Interest has been shown in the use of melanin nanoparticles (MNPs) for drug delivery applications. This study investigates the potential use of MNPs as an oral drug delivery system. The toxicity and cellular uptake of MNPs via intestinal barrier were evaluated using the Caco-2 cell model. Doxorubicin (DOX) was selected as a representative low bioavailability drug. The DOX-release profile of drug-loaded MNPs and molecular dynamic (MD) simulation were investigated at different pH. Our results demonstrated that MNPs synthesized from dopamine HCl are suitable as nanocarriers, presenting as monodisperse particles at mean size <300 nm. MNPs at size 89, 156, 268 nm at 3.13–50 μg/mL showed a high biocompatibiltity with Caco-2 cells, since no significant changes in %cell viability, reactive oxygen species, mitochondria membrane potential, and inflammatory cytokine were observed. The TEM results exhibited cellular internalization of MNPs into Caco-2 cells. The loading capacity (LC) and entrapment efficiency (EE) of DOX-loaded MNPs were 13.3 ± 2.7 % and 30.0 ± 3.6 %, respectively. DOX-loaded MNPs possessed a pH-dependent drug release profile. At pH 1.2, the amount of liberated DOX was 1.6- and 3.8-fold increase in comparison to pH 5 and 7.4, respectively. MD simulation clearly demonstrated that the binding affinity between polydopamines of MNPs and DOX molecules was weaker at the lower pH. These results thus support the potential use of MNPs as an oral drug delivery system particularly for drugs used in cancer treatment.