Arsip Mailing List Dokter Umum: [Dokter Umum] [Health News] Microbicides that do more than gel

Spotlight: Microbicides that do more than gel
Citizen News Service (CNS)
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A flexible ring containing two anti-HIV drugs showed in laboratory tests
that it can deliver therapeutic levels of both drugs for up to 30 days,
researchers reported at the International Microbicides Conference (M2010) in
Pittsburgh, USA, adding that they consider the ring near ready for testing
of its safety in women.

Vaginal rings have been used to deliver contraceptives and now this strategy
is being applied for delivering formulations of microbicides to protect
against HIV. Unlike gels that must be used every day or at the time of sex,
rings can be inserted into the vagina and stay in for a month or longer.
And, for certain drugs or drug combinations, these formulations may be the
more optimal vehicles for delivery.

Another option to deliver drugs with less fuss or muss, are quick-dissolve
films. In one study presented today, researchers described their progress in
developing a vaginal film – smaller than a stick of gum and as thin as a
sheet of paper – that after insertion into the vagina would melt away and
disperse drug to cells to protect against HIV. Laboratory tests of a similar
approach – an almond-shaped vaginal tablet – found the tablets dissolved
quickly yet still delivered sustained levels of anti-HIV drugs over several
hours.

Vaginal ring with two anti-HIV drugs nears benchmark for clinical testing of
its safety in women
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An intravaginal ring formulated with two anti-HIV drugs – dapivirine and
maraviroc – can deliver therapeutic levels of both drugs for as long as a
month, according to laboratory studies. Based on these and other findings,
the ring is a good candidate for testing in clinical safety trials, reported
Andrew Loxley, Ph.D., from Particle Sciences, Inc., of Bethlehem, Pa.
Vaginal rings are small, flexible devices designed to allow for the slow
delivery of a drug or multiple drugs over time. As a potential method for
preventing sexual transmission of HIV, rings are seen as an alternative to
microbicide gels that must be used every day or at the time of sex.
Dapivirine, also known as TMC-120, belongs to a class of anti-HIV drugs
called non-nucleoside reverse transcriptase inhibitors that bind to and
disable HIV's reverse transcriptase enzyme, a protein that HIV needs to make
more copies of itself. Maraviroc is a type of drug called an entry inhibitor
that prevents HIV from entering a healthy cell. The current study indicates
that inside the vaginal ring, the two drugs work well side-by-side with the
activity and structure of each drug not being affected by the presence of
the other. High amounts of each drug were still being released from the ring
at 15 days and continued to be delivered for up to 30 days. Even after being
stored in harsh conditions for six months, both drugs maintained their
stability and structure, suggesting that under more normal temperature
conditions, the rings remain viable for a year or even longer. The rings are
made of a type of plastic called ethylene-vinyl acetate copolymer (EVA) and
share many of the same properties as rings currently used for contraception.
They are manufactured using standard processes called hot metal extrusion
and injection molding. If clinical trials prove the rings safe and
effective, manufacturing and scale-up should be relatively easy, say the
researchers who made the rings with the support of the International
Partnership for Microbicides (IPM).

Early studies suggest promise for vaginal tablet containing ARV combination
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Seeking an alternative to microbicides in the form of the more traditional
gel, researchers have developed an almond-shaped vaginal tablet that
according to laboratory tests can dissolve quickly and deliver sustained
levels of anti-HIV drugs over 12 hours. Additional studies will be needed
before it can be considered for testing in clinical trials for its safety
and effectiveness for preventing sexual transmission of HIV in women,
reported Dr Sanjay Garg, Ph.D., an associate professor in the School of
Pharmacy, Faculty of Medical and Health Sciences, at the University of
Auckland in New Zealand. The research, which was conducted in collaboration
with the International Partnership for Microbicides (IPM) focused on
combining two antiretroviral (ARV) drugs – dapivirine, a non-nucleoside
reverse transcriptase inhibitor; and an entry inhibitor called DS003 – into
a vaginal tablet formulation. Dapivirine has already been formulated as a
vaginal ring and a gel, both of which are being tested in early phase
clinical trials, while DS003 (BMS 793) is in earlier development as a
candidate microbicide. The vaginal tablet is based on a pharmaceutically
acceptable bioadhesive polymer that binds to the moist lining inside the
vagina, allowing the drug to transfer to key cells that comprise the
epithelium. In their studies, Dr. Garg and colleagues demonstrated it is
feasible to formulate a vaginal tablet containing the two ARVs and that the
formulation is stable and the drugs are compatible. Moreover, they showed
that the tablet dissolves within three minutes yet the steady, slow delivery
of drug was sustained for several hours from the dispersion formed. Next
steps include performing toxicology studies of the vaginal tablet.

Vaginal film with novel dual-action ARV passes early laboratory tests
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IQP-0528 is a new antiretroviral (ARV) compound that although is classified
as a non-nucleoside reverse transcriptase inhibitor, works against HIV in
two ways. It prevents HIV from entering a cell and inhibits the activity of
reverse transcriptase, a key enzyme that HIV needs in order to make more
copies of itself. Now, researchers report they have developed a potential
microbicide containing this novel ARV. But rather than formulate the drug as
a traditional gel, the researchers created a vaginal film smaller than a
stick of gum and as thin as a sheet of paper. Laboratory tests indicate it
is potent against HIV, non-toxic to cells and that it can dissolve quickly
to release nearly all the compound. The results suggest the film formulation
is worth further study as a topical microbicide for the prevention of HIV
infection, reported Anthony Ham, Ph.D., who led the study for ImQuest
BioSciences of Frederick, Md. The film is made of a thin polyvinyl alcohol
polymer, a water-soluble synthetic plastic used in multiple consumer and
biomedical products, including contraceptive films, contact lens solutions
and mouthwash strips. Many believe that when it comes to a microbicide for
preventing HIV, women will prefer using a vaginal film over a gel,
especially if a long-acting formula allowed for less frequent use. To
evaluate the potential of IQP-0528 as a vaginal film, the researchers
performed a series of tests. In those looking at its antiviral activity,
IQP-0528 films were found effective against multiple strains of HIV. Other
tests indicated the film was not toxic to cells and had no negative effect
on normal vaginal flora. The film visibly disintegrated in solution within
10 minutes and within the same time period a sufficient level of drug was
released from the film to have activity against HIV. Results of these early
laboratory tests are encouraging but will need to be validated in further
studies.