Development of a Bioreactor to Simulate Drug Adsorptionfrom the Small Intestines into the Blood Stream

Biological Systems Engineering, Virginia TechHungry Hippos Engineering

David Morgan, Kevin Richter, Neil TempletonProblem StatementTo improve patient safety in oral pharmaceuticals a bioreactor will be developed to simulate drug adsorption from the small intestines into the blood stream.

This system will improve understanding of drug delivery considering aspects such as adsorption, chemical reactions, enzyme kinetics.

Components of SystemStomach: Contains pH of 1 with a flow rate of 5 mL/s. Will be modeled by a BioFlow 150 Reactor. This will simulate the initial phase of drug adsorption.Small Intestines : Contains a pH of 4-5 and will simulate how much of the drug will be adsorbed into the blood stream. This will be represented by a perforated cylinder filter.Blood Stream: Will simulate where Captopril will inhibit the enzymes. This will be represented by Affinity Chromatography with the enzymes (ACE) immobilized in the column.

Future Work If design can produce the in vivo measured rate

constants already known, then the ability to predict a drug’s performance in the human body exists

Proper Dosage: Increased SAFETY with less side effects, less allergic reactions

NIH funds could make this a senior design next year and incorporates a biomedical focus into BSE

Captopril One of the most popular blood pressure medications on

market today Captopril works by competitive enzyme inhibition 47% of current drugs on the market work by enzyme

inhibition Captopril inhibits Angiotensin Converting Enzyme (ACE) ACE converts Angiotensin I into Angiotensin II Compared to Angiotensin I, Angiotension II is 3x as

powerful in blood vessel constriction Therefore if ACE is restricted, blood pressure decreases

Justification for Research About 73.6 million American have high blood

pressure. In 2005, 57,356 deaths in the United States were

caused by high blood pressure. In 2002, Americans spent $12 billion dollars on high

blood pressure medication About 30-50% of total drug development costs go

toward clinical trials. This represents a monetary value of 50 – 300 million

dollars, varying on the type of drug.

What is the price of safety?

Enzyme Inhibitors, 47%

Transmembrane Receptors; 30%

Ion Channels; 7%

Other Receptors; 2% Nuclear Receptors; 2% Integrins; 1% DNA; 1%Miscellaneous; 1%

Product Price ($)HCl (2 L) 160Captopril (50 mg) 237Instant Breakfast (60 g) 23 pumps 9000Chromatography Column 8000Membrane (1 m2) 2000ACE (100 mg) 305000Vessel 25000Mixing/Storage Tank 400Millipore Sterile Syringe Filter 4Total $349803

Special thanks to Dr. Mike Zhang for his assistance and support