Fat for better drug function

Sci­en­tists have long known that food diges­tion affects the way the body absorbs var­ious compounds—from nutri­ents to drugs and toxins.

“You can get mul­tiple hun­dreds of per­cent improve­ment in bioavail­ability if you dose a com­pound in the pres­ence of a high fat mol­e­cule,” said Rebecca Car­rier, an asso­ciate pro­fessor of chem­ical engi­neering at North­eastern University.

The problem with that approach, how­ever, is that its unpre­dictability pre­vents doc­tors from using that knowl­edge to reduce drug dosages and improve drug delivery. “We don’t know when it’s going to happen and when it’s not going to happen,” Car­rier explained. “It’s not amenable to any form of quan­ti­ta­tive pre­dic­tion at this point.”

But that may soon change.

Car­rier has recently received a $1.8 mil­lion grant from the National Insti­tutes of Health with the hope of under­standing the mech­a­nisms behind this phe­nom­enon. “We want to develop pre­dic­tive models for how ingested lipids, or fat mol­e­cules, change the way your body absorbs dif­ferent com­pounds,” she said.

Drugs and nutri­ents, such as vit­amin B6, are often insol­uble in water. Since approx­i­mately 50 to 65 per­cent of the adult body is made up of water, these com­pounds have a hard time making their way into the blood stream. When lipids are nearby, they engulf these com­pounds and increase their solubility.

As Car­rier put it, “When you ingest some­thing, it changes the envi­ron­ment that the drug mol­e­cule sees.”

The project will ben­efit from the exper­tise of two other North­eastern fac­ulty members—Mansoor Amiji, Dis­tin­guished Pro­fessor and Chair of the Depart­ment of Phar­ma­ceu­tical Sci­ences, and David Budil, asso­ciate pro­fessor of chem­istry and chem­ical biology and asso­ciate dean for research in the Col­lege of Sci­ence.

Amiji will assist the Car­rier group with under­standing the rela­tion­ship between lab­o­ra­tory results and phe­nomena in the body. Budil, for his part, will use his exper­tise in chem­ical analysis to help Car­rier track the loca­tion of the body’s drug molecules.

Budil’s work will examine the body’s overall absorp­tion of drugs, but the phe­nom­enon is a cul­mi­na­tion of many dif­ferent fac­tors, including gas­troin­testinal mucus.

Exploring the prop­er­ties of the GI mucus bar­rier is the focus of another of Carrier’s projects, which is being sup­ported by a dif­ferent NIH grant. Car­rier noted that the prop­er­ties of the GI mucus bar­rier “are sig­nif­i­cantly mod­u­lated by stimuli asso­ci­ated with eating.”

“GI mucus is a very inter­esting hydrogel,” she added. “It is able to pro­tect you from this crazy envi­ron­ment of mil­lions and mil­lions of microor­gan­isms yet effi­ciently allows absorp­tion of all the com­pounds you need.”