Microneedles for oral mucosal delivery - Current trends and perspective on future directions.

INTRODUCTION: Oral cavity drug and vaccine delivery has the potential for local targeting, dose reduction, minimization of systemic side effects, and generation of mucosal immunity. To overcome current limitations of delivery into the oral cavity mucosa, microneedles (MNs) have emerged as a promising technology. AREAS COVERED: We reviewed the literature on MN application in the oral cavity, including in vitro studies, in vivo animal studies, and human clinical trials. EXPERT OPINION: MNs are sufficiently robust to cross the oral cavity epithelium and nearly painless when applied to different parts of the human oral mucosa including the lip, cheek, tongue, and palate. In recent years, MNs have been evaluated for different applications, including vaccination, topical anesthetic delivery, and treatment of local oral pathologies such as oral lesions or carcinomas. MNs are attractive because they have the potential to produce a better treatment outcome with reduced side effects. Over the coming years, we project a significant increase in research related to the development of MNs for use in dentistry and other medical conditions of the mouth.

Sex Dimorphism in Resolvin D5-induced Analgesia in Rat Models of Trigeminal Pain.

Resolvin D5 (RvD5) is a specialized pro-resolving lipid mediator with potent anti-inflammatory and analgesic properties. Orofacial pain conditions, especially those that are chronic, present clinical challenges in terms of pharmacological management. Thus, new therapeutic options are clearly warranted. Herein, we investigated the antinociceptive effect of RvD5 in the chronic constriction injury of the infraorbital nerve (CCI-ION) model and in the orofacial formalin test in female and male Wistar rats. Our results indicated that repeated subarachnoid medullary injections of RvD5 at 10 ng resulted in a significant reduction of heat and mechanical hyperalgesia induced by the CCI-ION in male and female rats, but males were more sensitive to RvD5 effects. In addition, after CCI-ION, interleukin-6 (IL-6) level was increased in the trigeminal nucleus caudalis of male, but not female rats, which was reduced by RvD5 repeated treatment. No changes in the levels of IL-1ß were found. Minocycline blocked the effect of RvD5 in male rats but failed to affect RvD5 antinociceptive effect in females. Moreover, a single medullary injection of RvD5 caused a significant reduction of formalin-induced facial grooming, in phases I and II of the test, but only in male rats. This study demonstrated for the first time the analgesic effect of RvD5 in trigeminal pain models, and corroborated previous evidence of sex dichotomy, with a greater effect in males. This article presents a translational potential of RvD5 for targeted therapies aiming at the control of acute and chronic trigeminal pain, but further studies are needed to elucidate its sex-related mechanisms. PERSPECTIVE: This study demonstrated that RvD5 may provide the benefits for trigeminal neuropathic pain treatment in male and female rats, but its effect on inflammatory orofacial pain seems to be restricted only to males. Also, it provided the evidence for sex dichotomy in the mechanisms related to the antinociceptive effect of RvD5.

Effects of lidocaine and the inclusion complex with 2-hydroxypropyl-ß-cyclodextrin on cell viability and proliferation of oral squamous cell carcinoma.

OBJECTIVES: Squamous cell carcinoma (SCC) is a malignant disease that affects the oral cavity. Lidocaine has shown antiproliferative and cytotoxic activity on several cell types. The rapid dispersion is a limitation issue; however, the complexation in cyclodextrin improved pharmacological features and modified the drug release. This study investigated the effects of lidocaine (lido) complexed with 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD-lido) on cell viability and proliferation of human tongue squamous cell carcinoma SCC9 and SCC25. METHODS: The complex formation was confirmed by differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). Cells SCC9 and SCC25 were exposed to lido and HP-ß-CD-lido (40-4000 µm), and the effects on cell viability (MTT) and antiproliferative activity (SRB) were tested. KEY FINDINGS: Differential scanning calorimetry and SEM results demonstrated the occurrence of host-guest interaction. Lido and HP-ß-CD-lido (4000 µm) significantly reduced the viability of SCC9 cells to 83% and 63%, respectively. The viability of SCC25 treated with lido, and HP-ß-CD-lido (4000 µm) was 71% and 44%, respectively. Lido (4000 µm) reduced the proliferation of SCC9 and SCC25 to 39.5% and 23.7%, respectively. HP-ß-CD-lido (4000 µm) was cytotoxic for both cell lines. CONCLUSIONS: HP-ß-CD was able to potentiate the in vitro cytotoxic effects of lidocaine on human squamous cell carcinoma.

The influence of altered occlusion on pro-inflammatory cytokine levels in the TMJ synovial tissues of rats.

OBJECTIVE: The aim of this study was to evaluate whether altered occlusion affects both the condylar cartilage thickness and the cytokine levels of the TMJs of rats. DESIGN: Thirty adult-male rats (n=30) were randomly assigned to three experimental conditions: a control group that underwent sham operations with unaltered occlusion; an FPDM group that underwent functional posterior displacement of the mandible that was induced by an incisor guiding appliance; and an iOVD group in which the increased occlusal vertical dimension was induced in the molars. The rats were subjected to the FPDM or iOVD model for 14 days and then killed. Both the right and left TMJs were removed and randomly assigned to examination with staining or immunoassay techniques. Toluidine blue staining was used to measure the thicknesses of the four layers of the articular cartilage (i.e., the fibrous, proliferating, mature, and hypertrophic layers). ELISA assays were used to assess the concentrations of the pro-inflammatory cytokines IL-1α, IL-1ß, IL-6, and tumour necrosis factor (TNF-α). The measurements of the articular cartilage layers and cytokine concentrations were analyzed with ANOVA and Tukey's tests and Kruskal-Wallis and Dunn tests, respectively (α=5%). RESULTS: The thickness of articular cartilage in the FPDM group (0.3±0.03mm) was significantly greater than those of the control (0.2±0.01mm) and iOVD (0.25±0.03mm) groups. No significant difference was observed between the control and iOVD groups. The four articular cartilage layers were thicker in the FPDM group than in the control and iOVD groups, and the latter two groups did not differ one from each other. Both the FPDM and iOVD groups exhibited higher cytokine levels than did the control (p<0.05) group. Compared to the FPDM group, the iOVD group exhibited significantly higher levels of IL-1ß and TNF-α. CONCLUSION: Both models induced inflammation in the TMJ and caused significant structural changes in the TMJ and surrounding tissues.