Olfactory Drug Delivery in Rodents: Deposition and Pharmacokinetics
Bibliographic record
Abstract
Olfactory drug delivery (ODD) is a route of administration that precisely targets the olfactory cleft, a region of the upper nasal cavity with privileged access to the brain. ODD offers better brain delivery compared to traditional intranasal (IN) delivery (e.g., nasal spray), which has imprecise, off-target drug deposition to the lower nasal cavities, with very little (if any) deposition at the olfactory region. ODD has immense potential for the noninvasive delivery of medication to the brain for the treatment of mental health and neurological disorders. Previously, we defined successful ODD as deposition of at least 50% of a dose to the olfactory cleft compared to the surrounding nasal cavities, assessed with a nasal endoscope. In this study, we investigate whether ODD is associated with increased brain uptake and compare the ODD, IN, and intravenous (IV) routes of administration across a range of compounds. First, using positron emission tomography (PET) imaging in rats, we demonstrate that ODD consistently targets the olfactory cleft, facilitating the brain uptake of fluorodeoxyglucose and fluorothymidine (FLT). These results successfully replicate previous work demonstrating direct nose-to-brain delivery of the poor blood-brain barrier penetrating molecule FLT. Additionally, we evaluated compounds that were selected for diversity of physiological properties and indications and demonstrated that for certain molecules, ODD offers superior brain delivery compared to IN and IV and demonstrates greater consistency than traditional IN administration. Remarkably, the volume of liquid required for ODD is approximately an order of magnitude smaller than that for the IN or IV methods, reducing variability in dosing, off-target deposition, and cost. These findings suggest that adopting the ODD method could enhance the accuracy, precision, and reproducibility of dosing across intranasal drug delivery applications. Importantly, ODD offers a consistent (less variable), accurate, and targeted method for improving the deliverability of medication to the brain.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".