ABSTRACT
Oral cancer, particularly squamous cell carcinoma (SCC), has posed a grave challenge to global health due to its high incidence, metastasis, and mortality rates. Despite numerous studies and favorable improvements in the therapeutic strategies over the past few decades, the prognosis of this disease remains dismal. Moreover, several drawbacks are associated with the conventional treatment; including permanent disfigurement and physical impairment that are attributed to surgical intervention, and systemic toxicity that results from aggressive radio- or chemotherapies, which impacts patients' prognosis and post-treatment quality of life. The highly vascularized, non-keratinized oral mucosa appears as a potential route for cytotoxic drug administration in treating oral cancer. It acts as a non-invasive portal for drug entry targeting the local oral lesions of the early stages of cancer and the systemic metastasis sites of advanced cancer. The absorption of the poorly aqueous-soluble anti-cancer drugs can be enhanced due to the increased permeability of the ulcerous mucosa lining in the disease state and by bypassing the hepatic first-pass metabolism. However, some challenges in oral transmucosal drug delivery include the drugs' taste, the limited surface area of the membrane lining the oral cavity, and flushing and enzymatic degradation by saliva. Therefore, mucoadhesive nanocarriers have emerged as promising platforms for controlled, targeted drug delivery in the oral cavity. The surface functionalization of nanocarriers with various moieties allows for drug targeting, bioavailability enhancement, and biodistribution at the site of action, while the mucoadhesive feature prolongs the drug's residence time for preferential accumulation to optimize the therapeutic effect and reduce systemic toxicity. This review has been focused to highlight the potential of various nanocarriers (e.g., nanoparticles, nanoemulsions, nanocapsules, and liposomes) in conferring targeting, solubility and bioavailability enhancement of actives and mucoadhesive properties as novel tumor-targeted drug delivery approaches in oral cancer treatment.
ABSTRACT
Many studies have been made on the distributions of CSF contacting neurons (CSF-CNs) in the parenchyma of the brain with horseradish peroxidase (HRP) or autoradiographics. A significant amount of data has shown that both HRP and autoradiographical substances could pass freely through the spaces of ependyma into the parenchyma of the brain. It is therefore possible that the results were not exact. We found that CB-HRP was a dependable tracer to CSF-CNs and studied the distributions and the signaling directions of cerebrospinal fluid contacting neurons (CSF-CNs) in the parenchyma of the brain with the cholera toxin subunit B with horseradish peroxidase (CB-HRP) tracing combined with transmission electron microscopy. The results were as follows: (1) CSF contacting tanycytes existed not only in the wall of the third ventricle (3V), but also in the walls of the lateral ventricle (LV), the fourth ventricle (4V) and the central canal (CC) of the spinal cord. (2) Some CSF contacting glia cells were observed in the lateral septal nucleus (LS). (3)The distal CSF-CNs in the parenchyma were found in LS, the anterodorsal thalamic nucleus (AD), the supramammillary nucleus (SuM), the dorsal raphe nucleus (DR), the floor of 4V and the lateral superior olive (LSO), but they were mainly found in DR and divided into groups A and B. (4) Axon terminals labeled by CB-HRP were found in the cavity of the brain ventricle. (5) The synaptic relationships between the neurons were labeled by CB-HRP in DR and no-labeled by CB-HRP in the parenchyma. Both synapses Gray I and II were found. It was significant that the presynaptic elements were formed by the neurons no-labeled CB-HRP and the postsynaptic elements labeled CB-HRP. Our results suggested firstly that the signaling directions of CSF-CNs in DR were only from the parenchyma to CSF.
