The overall goal of this procedure is to utilize an orally dissolvable bioadhesive polymer as a safe and human means of preclinical oral drug delivery. Using this procedure, a drug of interest can be incorporated into a flavored, orally dissolving strip for the oral administration of a test compound to an experimental animal. The main advantage of this technique is that it can be utilized instances when oral gavage isn't well tolerated.
To decrease stress during the ensuing drug administration procedures, allow the mice to acclimate to the husbandry conditions and handling technique of the experiment. For each mouse, determine the pre-experimental weight by grasping the mouse first by the middle of the tail, and gently lifting the animal out of the cage. Immediately place the animal into a weigh boat on an animal scale, keeping a firm grasp on the medial aspect of the tail to avoid a degloving injury and record the weight of the animal.
Record the weight of the food for a recommended two consecutive days to establish the baseline food consumption of each animal during the habituation period as well. After the animals have become acclimated to their environment transfer the animals to the room in which the subsequent experiments will occur. Before beginning the experiment, autoclave sterilize two stainless steel gavage needles per group, and one additional needle for back up.
Next, use a commercially available single quarter inch hole puncher to cut 0.5 centimeter diameter orally dissolving strips, or ODS, for each animal from a standard rectangular test strip. On the day of the experiment, record the weight of the animals as just demonstrated and then place the first mouse onto a metal grid cage top. Pull back on the tail with the dominant thumb, index, and third finger.
The mouse will grip the cage top and stretch out its back. Grasp the scruff of the neck with the non-dominant thumb, index finger, and third finger, to comfortably restrain the animal with a secure grip, and turn the animal to an upright position. Note the color of the mucosal membranes.
A pink red appearance indicates the mouse is comfortably restrained. Now submerge the bulb tip of one of the gavage needles in freshly prepared 4.25%sucrose solution to serve as a tastant adhesive to the ODS. Then press down on an ODS with the bulb tip to attach the ODS to the needle tip, and place the strip near the nostrils and mouth to allow the animal to consume the film.
Alternatively, the strip can be placed directly onto the tongue for the mouse to swallow. Replace the needle mid-group during the drug dosing session to prevent the spread of infection. Here, the effects of gavage administered ivermectrine on preference drinking are shown.
As observed, ivermectine significantly reduces the 10%ethanol intake across the study compared to the placebo group. Compared to the control group however, the ethanol intake values of the placebo group are much too low, and thus may not accurately model social drinking behavior. When the same experiment is performed utilizing the ODS delivery system, there is no significant difference in the ethanol intake between the control and placebo treated mice, indicating that the ODS placebo group represents a valid control with which a comparison to the ivermectine group can be made.
Indeed, by these controls, ivermectine significantly and consistently reduces the 10%ethanol intake of the animals. After watching this video, you should have a good understanding of how to utilize an orally dissolving strip as a safe and humane means of oral drug delivery.
