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. 2021 Nov 10;13(11):1904. doi: 10.3390/pharmaceutics13111904

Figure 2.

Figure 2

The refined technique results in up to 21% of the dose in the olfactory bulbs, when administered at the olfactory region (study 1). (A) Sagittal view on a murine head with highlighted areas for catheter-based administration at either respiratory mucosa (RM) or olfactory mucosa (OM) with adjacent olfactory bulb (OB) as part of the brain. As previously described, a region-specific technique was developed with the aid of 3D-printed models of the murine nasal cavity reconstructed from CT scans of a mouse head [25]. (B) demonstrates the conventional technique using a pipette with usually a rather high volume, from 20 to 30 µL. With this method, no selective delivery to the respiratory or olfactory mucosa is possible. Therefore, the intranasal delivery (C) has been refined by using a catheter with an adjusted smaller administered volume, which can deliver the drug region-specific either at the olfactory or respiratory area. The aim of study 1 was to validate the region-specificity of the refined catheter-based technique with fluorescein in vivo. (D) 10 min after administration, the levels reached with the refined technique were significantly higher than achieved with the conventional method or IV delivery (* p < 0.04, Student’s t-test). At 30 min after administration at the olfactory region, 21.8 ± 5.34% of the dose was recovered at the olfactory bulbs while administration with a pipette at the nostrils resulted in only 1.5 ± 0.05% (n = 2; p = 0.0626) and intravenous (IV) delivery resulted in 0.7 ± 0.07% (n = 2; p = 0.0587). (E) Elevated levels of fluorescein were detected in serum after IV administration and after intranasal delivery with the conventional pipette-based method. (F) Interestingly, higher levels of traces of the intranasally administered doses were swallowed and ingested with the conventional method than with the refined method (conventional: 1.15 ± 0.804% vs. refined: 0.03 ± 0.078% vs. IV: 0.078 ± 0.078%). Due to the limited number of animals per group this study shows tendencies, but fails to demonstrate statistical significance (mean ± SEM; n = 2). (A–C) are adapted with permission from ref. [25]. 2021, Nicole Lange et al.