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Tumors located in the oral mucosa are challenging to treat since surgery can lead to aesthetic, speech, and salivation problems, radiotherapy alone is often ineffective, and systemic chemotherapy brings meaningful side effects to the patient. Here, we proposed to develop mucoadhesive chitosan nanoparticles entrapping the chemotherapeutic oxaliplatin (OXPt) and to evaluate ex vivo its penetration in porcine mucosa under both passive and iontophoretic topical treatments. OXPt-loaded chitosan nanoparticles presented a small hydrodynamic size (188 ± 20 nm), narrow distribution (PDI of 0.28 ± 0.02) and positive zeta potential (+44.8 ± 2.8 mV). These nanoparticles provided a "burst effect" on drug release followed by a longer-term controlled release. When applied to the oral mucosa, the chitosan nanoparticles increased 3-fold drug penetration, and this rate was maintained even when the mucosa was "washed" with a buffer to mimic salivation. Iontophoresis doubled the amount of OXPt transported to the mucosa. These amounts exceeded the dose required to cause cell death of an oral tumor cell line. Besides, chitosan nanoparticles increased the rate of cells that entered into apoptosis. In summary, this study points to the feasibility of topical therapy with chitosan nanoparticles, potentialized by the application of iontophoresis, to treat oral tumors., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In this study, the chemically crosslinked hydrogels of carboxymethyl chitosan and polyvinyl alcohol were fabricated by the free radical polymerization. Successful polymerization was confirmed by Fourier transform infrared spectroscopy, while x-ray diffraction, thermogravimetric analysis, and differential scanning calorimetric measurements helped in investigating crystallinity and thermal behavior of the products. Morphological characterization was performed by scanning electron microscopy. The increased incorporation of carboxymethyl chitosan and polyvinyl alcohol enhanced the swelling, drug loading, and in-vitro drug release while crosslinking agent acted inversely. The blanked hydrogels were cytocompatible while oxaliplatin loaded hydrogels showed dose-dependent controlled cytotoxicity against HCT-116 and MCF-7. Oral biocompatibility in albino rabbits showed that the hydrogel suspension was tolerable up to 3600 mg/kg as no toxic or histopathological changes were observed upon comparison with the control group. Results of the studies confirmed that the developed hydrogels can be a potential candidate for controlled oxaliplatin delivery and targeting in cancer therapy., (Copyright © 2018 Elsevier B.V. All rights reserved.)