Name: choosing the right route for compound delivery
Uploaded: 2016-09-15T11:02:02.000Z
Duration: 9 min 38 s
Channel: JoVE
Description: Compound delivery is a key part of many animal studies. The route used to give the compound can change how it is absorbed. Careful planning helps make sure the compound is delivered correctly. The substance itself also matters when a route is chosen. Its pH, viscosity, and concentration can all affect which method is best. These properties help guide the choice of administration route in a study.

K12 Standards

new-york-state-science-learning-standards

New York State Science Learning Standards

High School

Life Science

Structure and Function

HS-LS1-2.

Compound Administration II

All animal procedures described here must be conducted in accordance with institutional animal ethics guidelines and approved by IACUC. All procedures must follow the principles of the 3Rs—Replacement, Reduction, and Refinement—and must be performed by trained personnel.
1. Topical application 
<ol>
	<li>Anesthesia should be used when necessary to minimize pain and distress during preparation and application procedures.</li>
	<li>Before applying any ointments and creams, remove all fur from the area through the use of a depilatory cream or by shaving.</li>
	<li>Thoroughly clean and dry the skin.</li>
	<li>Apply the substance directly to the skin with a cotton-tipped applicator or via a directly-placed drop to avoid contact with the technician.</li>
	<li>For best results, apply several thin layers of ointment or cream opposed to a onetime application of a thick layer.</li>
	<li>Apply liquid by parting the hair and applying a drop on the exposed skin.</li>
	<li>When applying a substance topically, there is a chance of systemic absorption due to the animal grooming the area. Preventative measures should be taken to avoid accident ingestion or early removal of the substance. Small collars or shields are available to prevent the animal from reaching affected body parts. Individual housing may also be required to prevent allogrooming from cage mates.</li>
	<li>Animals may be housed individually only when necessary and for the minimum required duration; as single housing is a recognized stressor and potential confounding factor, its use must be scientifically justified and minimized.</li>
</ol>
<img alt="animal testing preparation; applying topical agent; laboratory procedure; mouse; research method" src="/files/ftp_upload/10388/10388fig1v2.jpg" data-altupdatedat="1784001604000" data-alt="Figure 1"> 
Figure 1. Topical application in mice.
2. Oral dosing
<ol>
	<li>When providing compounds to animals via feed or water, a minimum daily dose based on body weight must be calculated. The average weight of the mouse or rat strain being used in the experiment can be used to make the calculations, unless it is specified that each animal be weighed and the dose figured for each individual.</li>
	<li>For example, if the intended dose is 10 milligrams per kilogram per day, the average animal weight is 30 grams or 0.03 kilograms, and there are 5 animals in one cage.</li>
	<li>Multiplying these values gives the total amount needed per cage per day. The final amount is 1.5 milligrams per cage per day. This is the amount that should be present in the average daily intake for that cage.</li>
	<li>For protocols that require that food and/or water intake be precisely measured, animals need to be housed individually.</li>
	<li>Animals must have continuous access to feed, and ad libitum feeding should be provided where appropriate in accordance with study requirements.</li>
	<li>Specialized feed or treats can be manufactured to meet experimental needs.
	<ol>
		<li>Replace the standard diet with the formulated one, which allows the animals to ingest the compound throughout the day.</li>
		<li>The food may need to be replaced more frequently than standard food due to compound instability.</li>
	</ol>
	</li>
	<li>Substances may also be administered by dissolving them in the drinking water, allowing for the animals to receive a compound throughout the day
	<ol>
		<li>A small amount of sugar is added to the water to make it palatable. The exact amount to add is determined by the acceptance of the water by the mice. Use the smallest increment possible.</li>
		<li>The frequency of changing the water is dependent on the stability of the compound. Some substances may be light-sensitive or precipitate over time.</li>
	</ol>
	</li>
</ol>
3. Oral gavageprocedure
18-20 gauge x 1.5 inch straight or curved dosing needles are used for mice. For rats, 16-18 gauge x 2-3 inch straight or curved dosing needles are used. These are available as reusable stainless steel needles or as disposable needles. The disposable needles can have a metal or flexible plastic shaft with a silicone tip.
<ol>
	<li>Attach the dosing needle to a syringe selected based on the volume and viscosity of the test solution. For dosing thick liquids, a Luer lock syringe is preferred. These are generally available beginning with a 3 cc size that has 100 µl graduations. This may not be suitable for smaller volumes or when there is a need for exact-dose volumes at smaller increments.</li>
	<li>Affix the syringe to the needle such that the graduations on the barrel can be read without turning the needle. Once the needle has been placed into the esophagus, any rotation can rupture the esophagus, resulting in death of the animal.</li>
	<li>Fill a syringe with the appropriate volume of article to be administered (optimal volume = 5 ml/kg and maximum volume = 20 ml/kg)</li>
	<li>The proper restraint is essential for this procedure.
	<ol>
		<li>Manually restrain mice by grasping the skin at the base of the head and scruffing them. It is important that the body be held such that it is suspended in a straight line from the head to the tail. Any twisting of the body will impede the placement of the gavage needle into the esophagus.</li>
		<li>Grasp the scruff tightly so that the head has minimal side-to-side movement. The hindquarters must be stabilized to prevent body rotation.</li>
		<li>For gavaging a rat, grasp it over the shoulders using the index and middle fingers on each side of the neck, and the palm on the animal's back. The thumb, third, and fourth fingers should encircle the chest to prevent the animal from being able to move forward or backward. The position of the fingers on each side of the neck prevents the rat from turning its head.</li>
		<li>It is important that the body be in a straight line and not twisted to assist in the placement of the gavage needle without damage to the mouth, pharynx, esophagus, or stomach.</li>
		<li>Make sure the head does not have excess side-to-side movement.</li>
		<li>The hindquarters may be stabilized to prevent body rotation. This is accomplished by allowing the back feet to rest on the counter or cage top.</li>
		<li>During restraint, animals should be monitored to ensure normal respiration is maintained.</li>
		<li>Although oral gavage is commonly performed in conscious animals, light anesthesia may be considered in cases involving highly stressed or difficult-to-restrain animals, or when repeated dosing is required; however, its use should be carefully evaluated due to potential effects on physiological parameters.</li>
	</ol>
	</li>
	<li>Administration of the substance
	<ol>
		<li>Before dosing, measure the tube externally from the head to the sternum, mark it at the nose, and do not insert beyond this point to avoid stomach perforation.</li>
		<li>Position the needle with the curve facing downward and in line with the natural curve of the neck. Introduce the needle into the mouth from the right or left side, between the incisors and molars at an angle toward the back of the pharynx.</li>
		<li>Once the needle is in the oral cavity, tilt the head back using the gavage needle until the nose is pointed up. This is especially important when using straight needles. The needle should slide easily into the esophagus. Do not force the needle down. If any resistance is felt, back the needle out and try again.</li>
		<li>Once the needle is in position in the stomach, gently deposit the compound.</li>
		<li>Remove the needle, making sure that no rotation of the curved needle takes place. The gavage needle should be removed slowly and gently, in the same motion that it was introduced.</li>
		<li>If the animal begins to struggle, remove the dosing needle and restrain the animal more securely.</li>
		<li>While performing the procedure, if the animal shows signs of cyanosis or respiratory distress, or if there is solution flowing from its mouth, the dosing needle should be immediately removed and the animal released into its cage.</li>
		<li>In general, when gavaging rats and mice, particularly with a caustic substance, it is a recommended practice to initially deliver a small amount – to test for coughing – before the entire volume is given. That way, if the needle is incorrectly positioned, the volume delivered to the lungs is small and the animal has a better chance at recovery. </li>
	</ol>
	</li>
</ol>
<img alt="Lab animal handling technique; diagram; laboratory research; rodent administration procedure." src="/files/ftp_upload/10388/10388fig2v2.jpg" data-altupdatedat="1784001604000" data-alt="Figure 2"> 
Figure 2. Oral gavage in mice (left) and rats (right).
Key Terms and Definitions 
The two main administration routes are enteral (via the digestive tract) and parenteral (administered outside of the digestive tract). The choice of the administration route is primarily determined by the requirements of the study. The main advantage of parenteral dosing is that the compound is not subjected to hepatic metabolism, resulting in higher bioavailability. However, there are many experimental protocols that require the compounds to be administered orally to better mimic the natural intake of a substance. The best route to utilize is determined by the properties of the test compound. 
Oral dosing: Oral dosing is the most commonly used method of drug administration in humans. This is done with tablets, capsules, or liquid forms of medication. Tablets and capsule administration are impractical in rodents, so the common oral dosing for mice and rats is accomplished by either dissolving the compound in drinking water, using specialized food that incorporates the test compound into the formula, or by placing the compound in treats. When dosing via drinking water, sucrose is often added to the water to enhance palatability. However, it should be finely balanced to encourage normal water intake and not excessive drinking because of the sugary taste. 
Many studies have demonstrated that repeated oral gavage is stressful to both mice and rats. It is also labor-intensive for the animal care staff. There is commercially available feed that has commonly dosed compounds, such as fenbendazole, which is used to eliminate parasites in rodents, incorporated into it. Other companies provide medicated treats that contain anti-inflammatories, analgesics, antiparasitics, or antibiotics. Feed companies that manufacture the formulated diets for mice and rats will create specialized test diets to meet an experimental requirement. Many laboratories have formulated their own treats with the use of honey, peanut butter, or fruit-flavored gelatin. 
Oral dosing lacks precision because the intake of a compound is dependent on the acceptance of the food or water, the stability of the compound, and the number of animals present in the cage. However, if exact dosing is not critical to the experiment, this noninvasive method of dosing is best for the well-being of the animals. 
Oral gavage: Oral gavage is a much more precise method of enteral dosing, as it allows for the deposition of the compound directly into the stomach of the animal at a specific time and at a specified volume. However, training is required to ensure success. Proper restraint of the animal is crucial to the success of this technique. Injury to the oral cavity, pharynx, larynx, trachea, esophagus, and stomach can result from improper positioning of the head and the body. The animal must be tightly gripped, such that the head is unable to twist, to prevent such injuries. 
Dosing needles are available in reusable or disposable formats. Though costly, the use of disposable needles removes the threat of cross-contamination when dosing multiple animals. There are several sizes of gavage needles, ranging from 20-22 gauge for mice and 18-20 gauge for rats. The choice of needle is determined by the size of the animal, the volume of liquid, and the viscosity of the solution to be administered. 
Oral gavage should be performed on a conscious animal to decrease the possibility of placing the needle into the trachea. An animal that is conscious will retain the swallowing reflex as well as the gag reflex, facilitating the proper placement into the esophagus. A study was conducted demonstrating that precoating the gavage needle with sucrose induced the swallowing reflex and decreased the amount of time needed to pass the needle into the esophagus. 
Topical administration: A topical agent that is placed directly on the surface of the skin is generally intended to affect only the area to which it is applied. These can be creams, lotions, ointments, foams, or gels. As animals will tend to groom the area where the agent is applied, the toxicity of oral consumption must be considered. 
Topical agents are generally used to produce local effects; however, systemic absorption can occur depending on factors such as skin integrity, application area, concentration, exposure duration, and lipid solubility. Well-hydrated and thin skin layers will decrease the absorption time. 
When applying a substance topically, there is the chance for systemic absorption due to the animal grooming the area. Preventative measures should be taken to avoid accident ingestion or early removal of the substance. Small collars or shields are available to prevent the animal from reaching affected body parts. Individual housing may also be required to prevent allogrooming from cage mates. However, animals may be singly housed only when necessary and for the shortest duration; as it is a stressor and potential confounder, it must be justified and minimized.  
Questions that this video will help you answer 
The safest and most humane method of compound administration is through oral dosing if it is possible to incorporate it into the feed or water. Oral gavage is a precise dosing method but is also very stressful to the animal, and it requires technical proficiency. Topical administration is usually accomplished with little or no restraint of the animal, once the area is properly prepared. Careful consideration of the route of administration should factor in the potential stress to the animals.

compound administration ii

Source: Kay Stewart, RVT, RLATG, CMAR; Valerie A. Schroeder, RVT, RLATG. University of Notre Dame, IN
Compound administration is often an integral component of an animal study. Many factors need to be evaluated to ensure that the compound is delivered correctly. The route of administration affects the mechanisms of absorption. The characteristics of the substance to be introduced (the pH, viscosity, and concentration) may dictate which route of administration is selected.

Source: Kay Stewart, RVT, RLATG, CMAR; Valerie A. Schroeder, RVT, RLATG. University of Notre Dame, IN
Compound administration is often an integral ...

In many experiments, compounds are administered to animals via oral or topical routes to better mimic natural exposure.&#160; 
One common oral method is to mix the compound into the animal&#8217;s drinking water or feed. Palatability can be improved by adding small amounts of sucrose or other flavoring agents.&#160; 
A starting concentration of 10% sucrose can be used and adjusted based on intake or approved IACUC protocols and institutional guidelines. 
Sucrose is often added to enhance intake; however, it should be carefully balanced to support normal consumption without causing excessive drinking.&#160; 
Another approach is dosing through specialized feed.&#160; 
Commercially available diets containing pre-mixed compounds allow non-invasive and continuous dosing.&#160; 
While this method reduces handling stress, it is less precise because intake may vary depending on food consumption, compound stability, and the number of animals per cage.&#160; 
Therefore, it is most suitable when exact individual dosing is not required.&#160; 
Whenever possible, non-invasive methods such as dosing through feed or water are preferred to reduce stress. 
For dosing through feed, calculations can be based on individual body weight whenever feasible. 
In group-housed animals, cage-level calculations may be used based on the number of animals and average daily consumption if animals are of similar size. 
For example, if the intended dose is 10 milligrams per kilogram per day, the average animal weight is 30 grams or 0.03 kilograms, and there are 5 animals in one cage.&#160; 
Multiplying these values gives the total amount needed per cage per day. The final amount is 1.5 milligrams per cage per day. This is the amount that should be present in the average daily intake for that cage.&#160; 
If medicated food or water is used, it may need to be replaced more frequently, particularly if the compound is unstable, light-sensitive, or prone to precipitation. 
When more accurate dosing is required, oral gavage can be used. In this method, a measured volume of the compound is delivered directly into the stomach. 
Select an appropriate gavage needle according to institutional guidelines. Options include reusable stainless steel needles or disposable flexible plastic feeding tubes with a silicone tip.&#160; 
Flexible plastic tubes are preferred as they reduce the risk of esophageal injury. 
For mice, use 18&#8211;20 gauge needles approximately 1.5 inches long. For rats, use 16&#8211;18 gauge needles approximately 2&#8211;3 inches long.&#160; 
Needle and syringe selection should also consider dose volume and viscosity, and a Luer lock syringe is recommended for viscous solutions. 
Before dosing, measure the tube externally from the head to the sternum, mark it at the nose, and do not insert beyond this point to avoid stomach perforation. Attach the syringe so that graduations can be read without rotating the needle. 
This is important as once the needle has been placed into the esophagus any rotation can rupture the esophageal wall, resulting in death. Next, fill the syringe with the correct volume of the solution to be administered. 
Gavage should be performed only on conscious animals with an intact swallowing reflex, using proper restraint techniques and trained personnel to minimize distress and risk of injury. 
In mice, hold the scruff firmly while keeping the body aligned in a straight line to prevent twisting. The hindquarters should be stabilized to avoid rotation. In rats, stabilize the shoulders and chest to control movement. 
Once restrained, position the gavage needle with the curve facing downward, aligned with the natural curvature of the neck. Insert the needle through the gap between the incisors and molars, guiding it toward the esophagus.&#160; 
Gently tilt the head upward to facilitate passage. The animal may swallow as the tube advances. Once the tube reaches the stomach, deliver the compound slowly and withdraw the needle without rotation.&#160; 
Do not force insertion; if resistance is felt, withdraw and reposition. Monitor respiration throughout the procedure. If signs of distress, cyanosis, or fluid expulsion are observed, immediately remove the needle and return the animal to its cage. 
Another route of administration is topical application, where the compound is applied directly to the skin. These include creams, lotions, ointments, sprays, and gels.&#160; 
For topical application, the animal is first anesthetized using a fast-acting inhalant to minimize stress and discomfort and allow rapid recovery. 
Remove fur from the application area using a hair clipper, keeping the flat surface against the skin and shaving against hair growth to avoid cuts.&#160; 
Gently clean the area with water or an institutionally approved mild solution and dry with gauze.&#160; 
Apply the substance using a cotton-tipped applicator in several thin layers rather than a single thick layer. 
Topical agents are typically intended for localized effects, although systemic absorption may occur depending on skin condition, surface area, concentration, duration of exposure, and lipid solubility. 
To prevent accidental ingestion due to grooming, use a small collar or protective shield.&#160; 
To prevent allogrooming by cage mates, animals may be housed individually only when necessary and for the minimum required duration.&#160; 
Animals should be returned to social housing as soon as possible unless prolonged individual housing is scientifically justified and institutionally approved.&#160; 
Appropriate environmental enrichment should be provided during any period of individual housing to support animal welfare. 
Now that you have an understanding of these alternate routes of administration, let&#39;s see how they are being used in biomedical research. 
One of the important applications of oral gavage is precise administration of substances to study their direct effect on the gastrointestinal tract. Here, the researchers used this method to deliver a transformed probiotic yeast directly into the animal&#39;s stomach. 
&#160;And then they dissected the Peyer&#39;s patches, which are organized lymph nodules from the small intestine, to study the adherence of the delivered microorganism. 
The non-invasive oral route can be used to mimic the natural modus of food-borne infection. In this experiment, the scientist developed a model for oral transmission of Listeria monocytogenes in mice via ingestion of contaminated food.&#160; 
Following infection, the researchers harvested various organs like small intestine, colon, spleen, liver and gall bladder, to analyze spread of infection to these tissues. 
Lastly, some researchers are interested in studying the mechanism by which UV radiation may lead to sunburns. Here, the scientists used a topical route to apply a pharmacologic substance that induces production of epidermal melanin-a UV protective agent.&#160; 
Following that, they used a protocol that is similar to human studies to examine the protective effect of the topically applied agent against erythema induced by UV radiation. 
You&#39;ve just watched JoVE&#39;s second installment of compound administration methods dealing with oral and topical dosing. You should now understand how one can orally dose the animal using feed or water, and how one can perform the more precise oral gavage administration. Lastly, you should know the considerations and methods for topical administration and applications of these various techniques.

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choosing the right route for compound delivery

Compound delivery is a key part of many animal studies. The route used to give the compound can change how it is absorbed. Careful planning helps make sure the compound is delivered correctly.

The substance itself also matters when a route is chosen. Its pH, viscosity, and concentration can all affect which method is best. These properties help guide the choice of administration route in a study.

Choosing the Right Route for Compound Delivery

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Learn how route of administration, pH, viscosity, and concentration affect compound delivery in animal studies and help guide the best method.

Choosing the Right Route for Compound Delivery | JoVE K12

HS-LS1-3.

Kay Stewart

Valerie A. Schroeder

University of Notre Dame

Overview

Oral Dosing via Feed or Water

Oral Gavage Procedure

Topical Application

Applications

Summary

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Translation

Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes ...

Ribosomes

Ribosomes translate genetic information encoded by messenger RNA (mRNA) into proteins. Both prokaryotic and eukaryotic cells have ribosomes. Cells that ...

Protein and Protein Structures

Proteins: From Genes to Degradation

From DNA to Protein

The flow of genetic information in cells from DNA to mRNA to protein is described by the central dogma, which states that genes specify the sequence of ...

Protein Folding

Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to ...

An Overview of Gene Expression

Gene expression is the complex process where a cell uses its genetic information to make functional products. This process is regulated at multiple ...

an-introduction-to-caenorhabditis-elegans

An Introduction to Caenorhabditis elegans

Caenorhabditis elegans is a microscopic, soil-dwelling roundworm that has been powerfully used as a model organism since the early 1970&rsquo;s.  It was ...

An Overview of Genetic Analysis

An organism&#8217;s physical traits, or phenotype, are a product of its genotype, which is the combination of alleles (gene variants) inherited from its ...

An Introduction to Cell Death

Necrosis, apoptosis, and autophagic cell death are all manners in which cells can die, and these mechanisms can be induced by different stimuli, such as ...

An Overview of Genetic Engineering

Genetic engineering &#8211; the process of purposefully altering an organism&#8217;s DNA &#8211; has been used to create powerful research tools and model ...

An Introduction to Cell Division

Cell division is the process by which a parent cell divides and gives rise to two or more daughter cells. It is a means of reproduction for single-cell ...

An Overview of Genetics and Disease

Many human diseases are associated with mutations or variations in genetic sequences. Some of these genetic variants are heritable, passed down from ...

an-introduction-to-cellular-and-molecular-neuroscience

An Introduction to Cellular and Molecular Neuroscience

Cellular and molecular neuroscience is one of the newest and fastest growing subdisciplines in neuroscience. By investigating the influences of genes, ...

Annexin V and Propidium Iodide Labeling

Staining with annexin V and propidium iodide (PI) provides researchers with a way to identify different types of cell death&#8212;either necrosis or ...

an-introduction-to-developmental-genetics

An Introduction to Developmental Genetics

Development is the complex process through which a single-celled embryo transforms into a multicellular organism. Developmental processes are guided by ...

Bacterial Transformation: Electroporation

The term &#x201C;transformation&#x201D; refers cellular ingestion of foreign DNA.  In nature, transformation can occur in certain types of bacteria.  In ...

an-introduction-to-molecular-developmental-biology

An Introduction to Molecular Developmental Biology

Molecular signals play a major role in the complex processes occurring during embryonic development. These signals regulate activities such as cell ...

bacterial-transformation-the-heat-shock-method

Bacterial Transformation: The Heat Shock Method

Transformation is the process that occurs when a cell ingests foreign DNA from its surroundings. Transformation can occur in nature in certain types of ...

an-introduction-to-saccharomyces-cerevisiae

An Introduction to Saccharomyces cerevisiae

Saccharomyces cerevisiae (commonly known as baker&rsquo;s yeast) is a single-celled eukaryote that is frequently used in scientific research.  S. ...

Cell Cycle Analysis

Cell cycle refers to the set of events through which a cell grows, replicates its genome, and ultimately divides into two daughter cells through the ...

An Introduction to Transfection

Transfection is the process of inserting genetic material, such as DNA and double stranded RNA, into mammalian cells. The insertion of DNA into a cell ...

Chromatin Immunoprecipitation

Histones are proteins that help organize DNA in eukaryotic nuclei by serving as &#8220;scaffolds&#8221; around which DNA can be wrapped, forming a complex ...

An Overview of Epigenetics

Since the early days of genetics research, scientists have noted certain heritable phenotypic differences that are not due to differences in the ...

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Community DNA Extraction from Bacterial Colonies

Source: Laboratories of Dr. Ian Pepper and Dr. Charles Gerba - The University of Arizona
Demonstrating Author: Luisa Ikner
Traditional methods of analysis ...

Cytogenetics

Cytogenetics is the field of study devoted to chromosomes, and involves the direct observation of a cell&#8217;s chromosomal number and structure, ...

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Embryonic Stem Cell Culture and Differentiation

Culturing embryonic stem (ES) cells requires conditions that maintain these cells in an undifferentiated state to preserve their capacity for self-renewal ...

DNA Gel Electrophoresis

DNA gel electrophoresis is a technique used for the detection and separation of DNA molecules. An electric field is applied to a gel matrix comprised of ...

Enzyme Assays and Kinetics

Enzyme kinetics describes the catalytic effects of enzymes, which are biomolecules that facilitate chemical reactions necessary for living organisms. ...

DNA Ligation Reactions

In molecular biology, ligation refers to the joining of two DNA fragments through the formation of a phosphodiester bond.  An enzyme known as a ligase ...

explant-culture-for-developmental-studies

Explant Culture for Developmental Studies

Explant culture is a technique in which living cells or tissues are removed from an embryo for continued development outside of the organism. This ex vivo ...

DNA Methylation Analysis

Methylation at CpG dinucleotides is a chemical modification of DNA hypothesized to play important roles in regulating gene expression. In particular, the ...

Expression Profiling with Microarrays

Microarrays are important tools for profiling gene expression, and are based on complementary binding between probes that are attached to glass chips and ...

Density Gradient Ultracentrifugation

Density gradient ultracentrifugation is a common technique used to isolate and purify biomolecules and cell structures. This technique exploits the fact ...

F&#246;rster Resonance Energy Transfer (FRET)

F&#246;rster resonance energy transfer (FRET) is a phenomenon used to investigate close-range biochemical interactions. In FRET, a donor photoluminescent ...

Construct an explanation based on evidence for how the structure of DNA determines the structure of proteins which carry out the essential functions of life through systems of specialized cells.

HS-LS1-1.

Choosing the Right Route for Compound Delivery

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