New
NRTI Microbicide Looks Promising in Lab
SUMMARY
A novel vaginal microbicide gel containing the reverse
transcriptase inhibitor IQP-0528 demonstrated good antiviral
activity and safety in laboratory studies. |
By
Liz Highleyman
Researchers
are working on several biomedical HIV prevention strategies,
ranging from vaccines to pre-exposure prophylaxis (PrEP).
Microbicides containing antiretroviral drugs have received
considerable attention, especially given the promising results
from the CAPRISA
trial testing a tenofovir-based gel in women in South
Africa.
As
described in the April
2011 issue of Antimicrobial Agents and Chemotherapy,
Alamelu Mahalingam from the University of Utah and colleagues
evaluated the safety and antiviral efficacy of a pyrimidinedione
compound known as IQP-0528 being developed by ImQuest BioSciences.
This agent was selected for further development due to its
stability under physiologically relevant conditions, a wide
therapeutic window, and antiviral activity in the nanomolar
range.
The
researchers developed 2 vaginal gels formulations containing
IQP-0528, one using 3.0% hydroxyethyl cellulose, the other
0.65% Carbopol polymer. The properties of these gels were
evaluated in laboratory studies using cells lines and human
cervical tissue samples.
Results
 |
The
gels demonstrated physical and chemical stability for
3 months. |
|
The
3.0% HEC gel had the best potential bioavailability and
was selected for safety and activity evaluations. |
|
In vitro and ex vivo safety evaluations of 3.0% HEC gel
containing 0.25% IQP-0528 showed "no significant
loss in cell viability or significant inflammatory response." |
|
An
in vitro HIV-1 entry inhibition assay showed that this
formulation had a 50% effective concentration of 0.14
mcg/mL in culture media. |
|
In
ex vivo cervical tissue, the gel demonstrated "complete
protection against HIV infection." |
Based
on these findings, the researchers concluded, "these
results are encouraging and warrant further evaluation of
IQP-0528 gel formulations in in vivo models, as well as the
development of alternative formulations for the delivery of
IQP-0528 as a microbicide."
"[T]his
formulation is expected to provide complete protection against
infection with no significant toxicity or irritation to vaginal
tissue," they added in their discussion. They estimated
that the cost of the gel could be as low as 30 cents per dose,
making it affordable in resource-limited settings.
Investigator affiliations: Department of Pharmaceutics
and Pharmaceutical Chemistry, University of Utah, Salt Lake
City, UT; Department of Bioengineering, University of Utah,
Salt Lake City, UT; ImQuest BioSciences, Inc., Frederick,
MD; Department of Obstetrics, Gynecology, and Reproductive
Sciences, University of Pittsburgh, Magee-Womens Research
Institute, Pittsburgh, PA.
5/6/11
Source
A
Mahalingam, AP Simmons, SR Ugaonkar, et al. Vaginal microbicide
gel for delivery of IQP-0528, a pyrimidinedione analog with
a dual mechanism of action against HIV-1. Antimicrobial
Agents and Chemotherapy 55(4):1650-1660 (abstract).
April 2011.
