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Technology Available For License
Drug Delivery that Overcomes
P-glycoprotein Mediated Drug Efflux
A drug delivery system that overcomes the problems associated with P-glycoprotein mediated drug efflux. Disadvantages of Current Treatments:
P-Glycoprotein (P-gp) is a transport protein that effluxes a wide variety of structural y unrelated drugs out of cel s. The bioavailability of various anticancer drugs, anti-HIV drugs, calcium channel drugs, and other drugs which are substrates is limited by this efflux transporter. Over-expression of P-gp by tumor cel s confers multi-drug resistance. Efflux of many anticancer drugs including taxol, vincristine, vinblastine, actinomycin D, colchicines, and daunorubicin, from tumor cel s makes P-gp a major barrier to chemothera-py. High expression of this transporter on the blood-brain-barrier (BBB) restricts the entry into the brain of P-gp substrates such as anti-HIV drugs such as ritonavir, saquinavir, nelfinavir, and various anticancer drugs, and thus imposes a major chal enge in the treat-ment of various diseases of the brain. Expression of the efflux transporter on various body tissues and cel s not only influences the in vivo disposition of various therapeuti-cal y active drugs, but also greatly influences the drugs' pharmacokinetics. It has been known that inhibition of P-gp by various modulators can lead to improved bioavailability of drugs across the intestines, the kidneys, and the BBB. Various modulators that inhibit P-gp are often co-administered with other bioactive agents to increase bioavailability. However, use of these compounds is limited by their toxicity. To achieve P-gp inhibition, doses that result in high serum concentrations of the toxic inhibitor are required. Although various approaches have been studied to overcome P-gp mediated drug efflux, P-gp remains a major barrier to bioa-vailability, chemotherapy, and effective permeation of P-gp substrates into the brain and other tissues. Invention Details:
In response to these troublesome efflux issues, UMKC researchers have developed methods of: Converting drugs that are substrates for the P-gp transporter into derivatives not recognized by P-gp as substrates, preferably targeted to and recognized by an influx membrane transporter/receptor (such as a peptide, vitamin or other nutrient trans-porter). The efflux of such derivatives from cel s by the P-gp transporter is thereby eliminated or substantial y reduced while their transport into target cel s by one or more influx transporters/receptors can be effectively enhanced increasing the bioa-vailability of bioactive compounds that are P-gp substrates. Increasing the concentration of bioactive compounds that are P-gp substrates in sanctuary sites of a mammalian subject. Enhancing cel ular delivery of bioactive compounds that are P-gp substrates. Suggested Uses:
For use with various anticancer drugs, anti-HIV drugs, calcium channel drugs, and other drugs which are substrates limited by this efflux transporter. Advantages:
Inhibition of P-gp by various modulators can lead to improved bioavailability of drugs across the intestines, the kidneys, and the blood-brain barrier. Lower toxicity due to less drugs being administered. Please visit our website at: for a detailed description of this and other technologies. UMKC Office of Technology Transfer


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