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This confocal microscope image shows uptake of the
nanocrystals by cancer cells, a technique developed by researchers
at UB and RPCI.
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The system involves the use of nanocrystals
measuring about 100 nanometers of pure HPPH,
(2-devinyl-2-(1'-hexyloxyethyl) pyropheophorbide), a photosensitizer
currently in Phase I/II human clinical trials at RPCI for treating
various types of cancer.
The UB researchers found that the nanocrystals of
HPPH were taken up by tumors in vivo, with efficacy comparable to
conventional, surfactant-based delivery systems.
A patent has been filed on this work.
"In this case, the drug itself acts as its own
carrier," said Haridas Pudavar, Ph.D., UB research assistant professor
of chemistry and a co-author.
The nanocrystals present a major advantage over
methods of delivery involving other carriers, according to Paras
Prasad, Ph.D., SUNY Distinguished Professor in the Department of
Chemistry in UB's College of Arts and Sciences, executive director of
the institute and a co-author.
Because other delivery systems, especially those
containing surfactants, commonly used with HPPH and many other drugs,
may add to the toxicity in the body, they have been considered
imperfect solutions.
"Unlike formulations that require separate delivery
systems, once this drug is approved, no additional approvals will be
needed," said Prasad.
"Our published data in animal models demonstrate no
difference in drug activity with the nanocrystal formulation," said
Ravindra Pandey, Ph.D., Distinguished Professor of Biophysical
Sciences at RPCI and a co-author on the paper.
"This is a case where the easiest formulation works
the best," added Indrajit Roy, Ph.D., UB research assistant professor
of chemistry and another co-author.
The researchers found that because HPPH is
amphiphillic, i.e., partially soluble in water and oil, nanocrystals
of it will self-assemble, that is, in solution the molecules aggregate,
but not into such big clusters that they settle to the bottom.
"It's a controlled formation of a colloidally
stable suspension of nanosized crystals," explained Tymish
Ohulchanskyy, Ph.D., UB senior research scientist and a co-author.
The researchers originally were investigating
nanocrystals as a delivery method for hydrophobic dyes in bioimaging
applications, another promising use for nanocrystals that they
continue to pursue.
Further in vivo studies with HPPH nanocrystals are
being conducted by scientists at UB and RPCI, including Pandey and
Allan R. Oseroff, M.D., Ph.D., chair of the department of dermatology
at RPCI and in UB's School of Medicine and Biomedical Sciences.
The UB/RPCI team is exploring the use of the same
technique for delivering other hydrophobic drugs, including those used
in chemotherapy. |
