Professor Partch Pursues Research in Drug Overdose Remediation:
A New Venue for Particles in Biotechnology
for in vivo controlled and selective removal of overdosed drugs
from blood are virtually unknown, yet hold great potential for saving
lives. The drugs may be legal and administered by an MD, may be
the illegal "street" type, or even agents of bioterrorism. The opposite
technology, controlled time and targeted release of therapeutic
agents, is mature and employed in the delivery of several common
pharmaceuticals. This is a progress report on a pioneering interdisciplinary
effort being carried out by
CAMP Professor Richard Partch,
CAMP graduate student
Evon Powell ( who received a poster session award on this topic),
and several Co- Principal Investigators affiliated with the University
of Florida including one of Partch's former Clarkson Ph.D. students,
Visiting Professor Young-Hwan Lee from Kyungwon University in Seoul,
The goals of
this research are to prepare, characterize and evaluate the in vitro
and in vivo ability of several types of dispersed phases to absorb,
bind and/or otherwise detoxify some of the most commonly overdosed
chemicals that cause large numbers of deaths annually. Chemists
like Partch play a pivotal role in the preparation and surface activation
of particles that are undergoing evaluation by anesthesiologists
on the team.
phases under investigation include
microemulsions designed to absorb lipophilic toxin molecules. The
microemulsions may be stabilized by a monomeric or polymerizable
surfactant. Data in Figure 10
shows that the microemulsion (ME-I; ME-II) approach has merit. Note
the rapid lowering of the blood plasma concentration of a frequently
overdosed prescribed antidepressant. On the same scale, 100% of
cocaine is removed. The efficiency is limited by the composition
and amount of microemulsion employed. For example, one composed
of triglycerides and PEG removes 90% of 5 ÁM bupivacaine local anesthetic
from saline and 80% from each blood plasma and blood.
polymer microgels with pores filled with oil. In preliminary tests
this type of dispersed phase shows less promise for drug removal
than the microemulsion systems.
or hard shell particles with high surface area having molecularly
templated pores and/or with surfaces chemically modified, with binding
sites that target a molecular feature unique to a toxin in question
Dispersed phases (1 - 3), but with an enzyme incorporated into the
particle matrix capable of destroying an overdosed drug. Figure
11 shows that this option is viable. An "ideal" dispersed
phase for use in detoxification might be some combination of the
four types, as shown in Figure 12.
10.Percent efficiency of binding (removal) of a toxic antidepressant
from blood plasma by ethyl butyrate microemulsions
Kinetics of rapid destruction of toxic bupivacaine anesthetic by
microemulsion containing P450 enzyme.
12. Structure of a proposed "ideal" nanoparticle for remediation
of overdosed lipophilic chemicals from blood .
is focusing his organic chemical expertise on surface modification
of particles to achieve the goals of this project. The cores of
such particles include metal oxides as well as various organic biopolymers.
Figure 13 shows one structural concept that successfully
causes toxins to bind to carrier particles and thereby be deactivated.
The fundamental basis for the binding is strong intermolecular interaction
between electron deficient and electron enriched benzene rings.
His team has
prepared 5-15nm silica particles having surface areas greater than
800 m2/g (which bind negligible toxin) and with 80-100
covalently attached p electron deficient
acceptor benzene rings per particle. Particles with attached receptors
have very high affinity for toxin molecules such as bupivacaine
and cocaine, even when only 0.05% solids are administered. (See
Figure 14.) They are
also useful for removing overdosed polycyclic aromatic pharmaceuticals
and carcinogens, all of which have electron rich rings.
p-p binding concept is so successful
that pi acceptors are not only being attached to inorganic and biopolymer
latex particles, but are also being incorporated into the less efficient
microemulsion and microgel dispersed phases discussed. All of the
advances in the various approaches described have been made during
2001, and it is anticipated that in 2002 the dispersed phase giving
the best in vitro result will be evaluated in vivo. Beyond restoring
human health from an overdose of legally administered therapeutic
agents, the research program has the potential of producing nanoparticles
capable of detoxifying a wide variety of molecules used by addicts
and terrorist groups.