Development of a gel permeation chromatographic assay to achieve mass balance in cellulose acetate phthalate stability studies.

Cellulose acetate phthalate (CAP, cellulose acetate 1,2-benzenedicarboxylate) is a common polymeric oral tablet coating. CAP is also a vaginal microbicide candidate that potently inhibits HIV-1 proliferation. This paper describes the development of a precise, stability-indicating gel permeation chromatography (GPC) assay for CAP.

Anti-HIV-1 activity of poly(mandelic acid) derivatives.

Homo- and heterochiral poly(mandelic acid)s (PMDAs) were synthesized under strongly acidic, mildly acidic, and nonacidic conditions. The water-soluble fractions of these polymers were evaluated with respect to their inhibitory activity against the human immunodeficiency virus (HIV-1). Polymers were prepared via a step-growth mechanism, yielding linear polyesters.

Role of seminal plasma in the anti-HIV-1 activity of candidate microbicides.

Background: Evaluation of microbicides for prevention of HIV-1 infection in macaque models for vaginal infection has indicated that the concentrations of active compounds needed for protection by far exceed levels sufficient for complete inhibition of infection in vitro. These experiments were done in the absence of seminal plasma (SP), a vehicle for sexual transmission of the virus. To gain insight into the possible effect of SP on the performance of selected microbicides, their anti-HIV-1 activity in the presence, and absence of SP, was determined.

Punica granatum (pomegranate) juice provides an HIV-1 entry inhibitor and candidate topical microbicide.

For approximately 24 years the AIDS pandemic has claimed approximately 30 million lives, causing approximately 14,000 new HIV-1 infections daily worldwide in 2003. About 80% of infections occur by heterosexual transmission. In the absence of vaccines, topical microbicides, expected to block virus transmission, offer hope for controlling the pandemic.

Identification of N-phenyl-N'-(2,2,6,6-tetramethyl-piperidin-4-yl)-oxalamides as a new class of HIV-1 entry inhibitors that prevent gp120 binding to CD4.

We have identified two N-phenyl-N'-(2,2,6,6-tetramethyl-piperidin-4-yl)-oxalamide analogs as a novel class of human immunodeficiency virus type 1 (HIV-1) entry inhibitors that block the gp120-CD4 interaction, using database screening techniques. The lead compounds, NBD-556 and NBD-557, are small molecule organic compounds with drug-like properties. These compounds showed potent cell fusion and virus-cell fusion inhibitory activity at low micromolar levels.

Punica granatum (Pomegranate) juice provides an HIV-1 entry inhibitor and candidate topical microbicide.

Background: For approximately 24 years the AIDS pandemic has claimed approximately 30 million lives, causing approximately 14,000 new HIV-1 infections daily worldwide in 2003. About 80% of infections occur by heterosexual transmission. In the absence of vaccines, topical microbicides, expected to block virus transmission, offer hope for controlling the pandemic.

Water dispersible microbicidal cellulose acetate phthalate film.

Background: Cellulose acetate phthalate (CAP) has been used for several decades in the pharmaceutical industry for enteric film coating of oral tablets and capsules. Micronized CAP, available commercially as "Aquateric" and containing additional ingredients required for micronization, used for tablet coating from water dispersions, was shown to adsorb and inactivate the human immunodeficiency virus (HIV-1), herpesviruses (HSV) and other sexually transmitted disease (STD) pathogens. Earlier studies indicate that a gel formulation of micronized CAP has a potential as a topical microbicide for prevention of STDs including the acquired immunodeficiency syndrome (AIDS).

Anti-HIV-1 activity of anionic polymers: a comparative study of candidate microbicides.

Background: Cellulose acetate phthalate (CAP) in soluble form blocks coreceptor binding sites on the virus envelope glycoprotein gp120 and elicits gp41 six-helix bundle formation, processes involved in virus inactivation. CAP is not soluble at pH < 5.5, normal for microbicide target sites.

Anti-HIV-1 activity of cellulose acetate phthalate: synergy with soluble CD4 and induction of "dead-end" gp41 six-helix bundles.

Background: Cellulose acetate phthalate (CAP), a promising candidate microbicide for prevention of sexual transmission of the human immunodeficiency virus type 1 (HIV-1) and other sexually transmitted disease (STD) pathogens, was shown to inactivate HIV-1 and to block the coreceptor binding site on the virus envelope glycoprotein gp120. It did not interfere with virus binding to CD4. Since CD4 is the primary cellular receptor for HIV-1, it was of interest to study CAP binding to HIV-1 complexes with soluble CD4 (sCD4) and its consequences, including changes in the conformation of the envelope glycoprotein gp41 within virus particles.