Discovering a therapeutic agent is only the first step in developing a new drug. Even if the drug has immensely beneficial properties, it is virtually useless if it cannot enter the bloodstream.
Drug absorption and delivery is an obstacle to therapy that few researchers have been able to effectively tackle. That’s where Dr. Ping Lee, professor at the Leslie Dan Faculty of Pharmacy at U of T, comes in. Lee has dedicated his research to enhancing and modulating drug delivery. “We are concentrating on overcoming the problem of low solubility. If something doesn’t dissolve in the body, it won’t be absorbed—it’s that simple,” he says.
Soluble drugs dissolve readily in aqueous media, such as the gastrointestinal tract, where they can ultimately pass into the bloodstream. Alternatively, poorly soluble drugs remain in the lumen of the gastrointestinal tract, are not absorbed by the bloodstream, and are thus unavailable to the body. Therein lies the problem. Many otherwise beneficial drugs fall into the “poorly soluble” category of pharmaceutical agents.
But sometimes drug manufacturers will want to delay a drug from coming into full effect, even after it has been administered to the body. In such cases, researchers will set up additional, artificial barriers that the pharmaceutical agent will have to surpass before entering the bloodstream.
Lee has engineered a unique system of drug release modulation that embeds drugs in a polymer matrix that gradually releases drugs into the bloodstream. The implications of such a controlled-release system are monumental, as it may obviate multiple dosing medication regimens, replacing them with once-daily—or perhaps even less frequent—dosing.
The plate-like characteristics of Lee’s drug delivery system are crucial to its function. The polymers are like plate or glass when dry, but once in an aqueous medium (such as the gastrointestinal lumen) the system is hydrated, swells up, and forms a gel-like body. Hydration of the system leads to slow and controlled release of the drug.
The drug remains immobile until it is completely released into the bloodstream, when it then exerts its full effect. Lee explains, “Hydrophilic glassy polymers increase solubility by stabilizing the drug in its amorphous [disordered] form. The polymer prevents the drug from crystallizing, and its solubility is increased because it does not have to overcome the crystal lattice. This facilitates absorption in the intestine.”
Due to issues arising from the solubility of a drug, patients sometimes need to take multiple and frequent doses in order to experience the medication’s full therapeutic effect. Patient compliance with medication regimens is itself often a barrier to achieving maximal therapeutic benefit, and for good reason: it can be pretty inconvenient for patients to adhere to regimens which entail frequent dosing, as opposed to one pill a day, which is less likely to be overlooked.
The development coming out of Lee’s work holds larger scale promise for remedying absorption issues that have troubled medicinal chemists and halted the advancement of pharmaceutically active drugs for years. In addition to improving patient-drug adherence and the implied cost-savings for patients, this technology can be extrapolated to enhance the delivery of many pharmaceutical agents that otherwise do not enter the bloodstream easily.
