Abstract
A well-developed lymphatic network is located under the nasal mucosa, and a few drugs that permeate the nasal mucosa are absorbed into the lymphatic capillaries. Lymph from the nasal cavity flows to the cervical lymph nodes (CLNs). In this study, we evaluated the pharmacokinetics of the direct transport of intranasally administered drugs to CLNs through the nasal mucosa of Wistar rats using methotrexate as a model drug. The drug targeting index, which was calculated based on the areas under the concentration–time curves after intravenous and intranasal administration, was 3.78, indicating the benefits of nasal delivery of methotrexate to target CLNs. The direct transport percentage, which was indicative of the contribution of the direct nose–CLN pathway of methotrexate after intranasal administration, was 74.3%. The rate constant of methotrexate from the nasal cavity to CLNs was 0.0047 ± 0.0013 min−1, while that from systemic circulation to CLNs was 0.0021 ± 0.0009 min−1. Through pharmacokinetic analysis, this study demonstrated that the direct nasal–CLN pathway contributed more to the transport of methotrexate to the CLNs than the direct blood–CLN pathway.
Highlights
In the last few decades, the intranasal (i.n.) route of administration for systemic drug delivery has received considerable attention [1]
A well-developed lymphatic network is located under the nasal mucosa, and a few drugs that permeate the nasal mucosa are distributed through the lymph capillaries
We evaluated the pharmacokinetic profile of intranasally administered methotrexate (MTX) as a model drug in terms of its ability to be directly transported to the
Summary
In the last few decades, the intranasal (i.n.) route of administration for systemic drug delivery has received considerable attention [1]. The relatively high permeability of the nasal epithelium, its high vascularization in the lamina propria [4,5], and the ability to avoid hepatic first-pass metabolism render intranasal drug delivery a promising route for drug administration, especially for drugs that are metabolized in the intestine and/or liver [6]. A well-developed lymphatic network is located under the nasal mucosa, and a few drugs that permeate the nasal mucosa are distributed through the lymph capillaries. In the surgical treatment of tongue or pharyngeal cancers, is the primary tumor removed, but CLN dissection is performed because these lymph nodes are considered a common site for metastasis. The relationship between CLN dissection and patient prognosis is not fully understood, and there are advantages and disadvantages
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