Cytotoxic Effects of Drug-loaded Hyaluronan-Glutaraldehyde Cross-Linked Nanoparticles and the Release Kinetics Modeling

In this study, paclitaxel (PTX)-loaded hyaluronic acid (HA) nanoparticles (NPs) were synthesized. FESEM and TEM showed HA-PTX NPs with spherical shape and sizes >100 nm. TheHA entrapment maintained the crystalline nature of PTX as suggested by XRD, and the entrapment was confirmed by the characteristic peak of PTX at 1736 cm-1 by FTIR. HA-PTX showed cytotoxicity towards lung (A549) (IC50 0.3 μg/ml), breast (MCF-7) (IC500.2 μg/ml) and colorectal (HT-29) (IC50 0.2 μg/ml) cancer cells, with 2-3 fold more cytotoxic effects than free PTX. At 10 ng/ml in A549 cell lines, PTX induced apoptosis, whilst HA-PTX showed enhanced apoptosis. The release kinetics profile showed PTX release in a biphasic manner, with initial burst release of 60-70%, followed by a slow and uniform release. PTX release was best modeled by first-order kinetics, Higuchi and Korsmeyer-Peppas models suggesting that it was concentration dependent, with anomalous, non-Fickian diffusion as a predominant mechanism for the drug transport