Surgical and Non-Surgical Drug Delivery Methods in Miniswine Models

Authors

Buckman, K., Brown, L., Hanks, B.C., Stricker-Krongrad, A., Sword, M., Madsen, T., Lawson, C., Brocksmith, D., Liu, J., Bouchard, G.F.

Abstract

Miniswine models have evolved to become very important in the preclinical evaluation of drugs. Moreover, translational medicine programs are confirming that the minipigis the model of choice for pharmacokinetics assessment, in addition to its role in the evaluation of drug efficacy and safety.

Miniswines provide numerous advantages when conducting pharmacokinetics (PK) studies: their body size allows numerous blood samples with large volumes, their smaller body size as compared to domestic pigs facilitates their handling, their anatomy and physiology size-proportional when compared to humans and biotransformation factors (e.g. CYP450 enzymes) are similar to humans.

However, although most classical routes of exposure are possible in the miniswine, some do require the use of specialized drug delivery methods. Purpose: In the present report, we will illustrate selected surgical and nonsurgical drug delivery methods that can be applied to the minipig amongst the broad available array of delivery devices.

Methods: For example, vascular access in minipigs includes surgical and non-surgically placed catheters or direct venipuncture. Subcutaneous vascular access ports (VAPs) are placed surgically into the external jugular vein and may be placed bilaterally to facilitate both dosing and sampling. Repeated access of the port through the skin is possible using a specially designed needle (Huber point). Port useful lifetime in minipigs can be quite long but good port maintenance is essential. Troubleshooting of port malfunction includes assessment for infection, complete occlusion or partial withdrawal occlusion (PWO or fibrin flap).

Results: In addition, we will describe the feasibility and ease of use of the following devices:
Surgical Delivery Methods:Intestinal Delivery Cannulas, Femoral Catheters, Cardiac or Pericardial Catheters, Drug-Eluting Devices.

Non-Surgical Delivery Methods: Percutaneous Catheters, Infusion Catheters, Topical Delivery Pumps, Endoscopic Drug Delivery, Dermal Patches, Intrathecal and Intracisternal Catheters.

In conclusion, the use of the miniswine has been validated for pharmacokinetic modeling over the years and most drug delivery methods are compatible if adapted to their anatomy and physiology.

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