No abstract

Background and purposeXerostomia is frequently reported after radiotherapy (RT) for head and neck cancer (HNC). The aim of this study was to reduce symptoms of radiation-induced xerostomia in HNC survivors, in which the experimental arm used chewing gum for a month. Primary endpoint was changes in scoring of dry mouth as defined by EORTC QLQ-H&N35 between arms. Materials and methodsParticipants with any grade of physician-assessed xerostomia, ≥ six month after RT, disease-free and able to chew gum were, for a month, randomized (2:1) to: (Arm A) daily chewing gum or (Arm B) standard care.Xerostomia-related QOL was assessed using EORTC QLQ-H&N35 and GRIX questionnaires along with measurement of salivary flow and viscosity at inclusion and after one month. The study was registered on ClinicalTrials.gov (NCT03302676). ResultsNinety-one participants were eligible for analysis (Arm A, n=55; Arm B, n=36). Comparing categorized scores for symptoms between arms, reduction of dry mouth was significantly higher for Arm A than Arm B (p=0.05). A reduction in dry mouth scores was observed for xerostomia assessed by EORTC QLQ-H&N35 (question 41) for both arms. Salivary flow increased and viscosity decreased upon five minutes of stimulation within both arms (p<0.001, respectively), however no significantly difference was observed between arms. ConclusionCategorized scores found reduction of dry mouth to be significantly higher in Arm A than Arm B, but no difference was seen for salivary flow rate and viscosity.

Improved nicotine permeability across buccal mucosa may enable more effective oromucosal nicotine replacement therapy products. It is essential to know the location and composition of the main barrier for drug diffusion to enhance the drug permeability. Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MSI) is a rapidly evolving technique that can be used to image the spatial distribution of drugs and drug metabolites in tissue cryo-sections, without prior labeling of the drug. In this study, the distribution of nicotine and mannitol in porcine buccal mucosa was imaged with 10 μm spatial resolution after apical as well as submucosal application of the drugs in order to localize the main permeability barrier(s). This was supported by ex vivo permeability studies across separated porcine buccal epithelium and submucosa. Lastly, the metabolism of nicotine in porcine buccal mucosa was evaluated by imaging of the main metabolite, cotinine. The results showed that the main permeability barrier to both nicotine and mannitol was located in the outer fourth of the epithelium. Further, it was shown that cotinine was sparsely distributed in excised porcine buccal mucosa, indicating that nicotine metabolism in excised porcine buccal mucosa was negligible. MALDI MSI was shown to be a useful method for imaging spatial distribution of drugs in buccal mucosa.

No abstract

The buccal permeability of nicotine was affected in an enhancer specific manner, suggesting that nicotine primarily diffuses via the transcellular pathway. MALDI MSI was shown to complement ex vivo permeability studies and to be a useful qualitative tool for visualizing drug and penetration enhancer distribution in buccal mucosa.