This article describes methods for intranasal drug administration in anesthetized mice, focusing on techniques that enhance drug retention and transport to the brain. The procedures include micropipette-based delivery and reverse cannulation, each with specific steps to optimize drug absorption.
Take an anesthetized mouse in a supine position with an inhalation mask to provide anesthesia.
For pipette-based intranasal drug administration, take a micropipette containing a radiolabeled drug.
Insert the micropipette through an opening in the mask and administer the drug into the nasal cavity.
The cavity is lined with respiratory and olfactory epithelium, both of which contain cilia that actively clear substances, thereby limiting drug retention.
The retained drug molecules travel via nerves to reach the brain.
For intranasal drug administration via reverse cannulation, position the mouse under a microscope and make a neck incision.
Expose the trachea, incise it, insert a cannula, and connect it to the mask to maintain anesthesia.
Expose the esophagus, make an incision, and insert a cannula directed towards the nasal cavity.
Ligate the cannula and attach it to a syringe containing the radiolabeled drug.
Deliver the drug against the direction of ciliary motion, enhancing retention and improving drug transport.
For intranasal delivery via micropipette in an isolated radioisotope facility, tape an anesthetized mouse to a cork board in the supine position and administer 25 microliters of carbon-14 inulin solution in one to two microliter doses alternatively into the left and right nostrils of the animal.
For reverse cannulation delivery from the airway side through the esophagus, place the anesthetized mouse under a dissecting microscope and make a 1.5 skin incision over the throat. Use forceps to expand the incision until the trachea is exposed, and make a 1 millimeter incision in the exposed trachea. Insert a cannula 1.2 to the pre-marked position into the incision, and attach the opposite end of the cannula to the inside of an inhalation mask.
After this, use forceps to expose the esophagus from under the trachea. Use scissors to make a 1 millimeter incision in the esophagus, and insert a second cannula 1.4 to the pre-marked position toward the posterior end of the nasal cavity.
It is important to insert the cannula to an appropriate length according to the weight of the experimental animal, and to adjust the length of the cannula in other ones.
Ligate the esophageal cannula and attach a 27-gauge needle to a 1-milliliter syringe filled with an administration solution connected to a programmable micro syringe pump. Then deliver 25 microliters of carbon-14 inulin at a constant 5-microliter per minute rate until the entire volume of solution has been administered.
A slow but constant diffusion rate is important for the retention of as much drug solution as possible within the nasal cavity.
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