A cross-disciplinary team of researchers at the University of Maryland
has designed a molecular container that can hold drug molecules and increase
their solubility, in one case up to nearly 3000 times. Their discovery opens
the possibility of rehabilitating drug candidates that were insufficiently
soluble. It also offers an opportunity to improve successful drugs that could
be made even better with better solubility.
The team’s innovative findings were recently published in Nature Chemistry, in which the authors
note that “the solubility characteristics of 40% to 70% percent of new
drug candidates are so poor that they cannot be formulated on their own, so new
methods for increasing drug solubility are highly prized.“
The Maryland
scientists where able to increase the solubility of ten insoluble drugs by
between 23 and 2,750 times, by forming container-drug complexes. They also show
that their containers have low toxicity in human cell line and mice studies,
and that the molecular containers can be built from inexpensive and readily
available reagents.
“We already are working with drug companies to help them solubilize
their interesting drug candidates and hope to get them interested in licensing
our technology,” says co-leader Volker Briken, an associate professor in
the department of cell biology and molecular genetics and also a scientist in
the Maryland Pathogen Research Institute.
The team, led by Briken and UMD Chemistry and Biochemistry Professor Lyle
Isaacs, created their “new class of general-purpose solubilizing
agents” based on a type of compound called cucurbit[n]urils—or CB[n].
These are ‘macrocyclic’ molecules made up of units of bicyclic glycoluril C4H4N4O2
monomers. The n in CB[n] refers to the number of repeat units in the macrocycle.
Many previous attempts have been made to capture drug molecules within these
and other synthetic cages and capsules to increase drugs’ solubility, but with
limited success.
Issacs and Briken say that next their team would like to increase the
variety of novel acyclic CBs in order to be able to solubilize a maximal number
of small chemical drug candidates, and also would like to generate CBs that can
be specifically targeted—for example to cancer cells.
Filed Under: Drug Discovery
