Chitosan nanoparticles loading oxaliplatin as a mucoadhesive topical treatment of oral tumors: Iontophoresis further enhances drug delivery ex vivo.

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.