Effect of a Cellulose Acetate Phthalate Topical Cream on Vaginal Transmission of Simian Immunodeficiency Virus in Rhesus Monkeys

Abstract

Human immunodeficiency virus type 1 (HIV-1) infection continues to spread in developing countries, mostly through heterosexual transmission. The development of a safe and cost-effective topical microbicide, effective against a range of STDs including HIV-1, would greatly impact the ongoing epidemic. When formulated in a vehicle, a micronized form of cellulose acetate phthalate (CAP), which is an inactive pharmaceutical excipient, has been shown to inactivate HIV-1, herpes simplex virus types 1 and 2, cytomegalovirus, Neisseria gonorrhoeae, Trichomonas vaginalis, Haemophilus ducreyi, and Chlamydia trachomatis in vitro. Formulated CAP was also shown to be effective against herpes simplex virus type 2 in vivo. Here we show that a formulation of CAP protected four of six rhesus monkeys from vaginal infection with simian immunodeficiency virus. Thus, CAP may be a candidate for use as a topical microbicide for preventing HIV-1 infection in humans.

A Review of Current Intravaginal Drug Delivery Approaches Employed for the Prophylaxis of HIV/AIDS and Prevention of Sexually Transmitted Infections

“…It is converted into a gel and therefore does not have to be removed following its application (119). CAP is one of the potential anti-HIV vaginal gel formulations that are under Phase II clinical trials (120).…”

Use of Animal Models for Anti-HIV Drug Development

“…Compounds tested in macaque models have aimed to interfere with nonspecific viral attachment (Ambrose et al, 2008;Boadi et al, 2005;Kenney et al, 2011;Kim et al, 2006;Lagenaur et al, 2011;Li et al, 2009;Manson et al, 2000;Tevi-Benissan et al, 2000;Tsai et al, 2004;Wyand et al, 1999), specific interactions of envelope with receptor/co-receptors (KishCatalone et al, 2007;Lederman et al, 2004;Mascola et al, 2000;Parren et al, 2001;Veazey et al, 2008;Veazey et al, 2010;Veazey et al, 2003a;Veazey et al, 2005a;Veazey et al, 2009;Veazey et al, 2003b;Veazey et al, 2005b), and reverse transcription Parikh et al, 2009;Stolte-Leeb et al, 2011;Turville et al, 2008). Another study investigated hormone treatment, which leads to thickening of the vaginal epithelium, to prevent vaginal transmission of SIV in macaques (Smith et al, 2000b).…”

In-vitro Antiviral Activity of a Novel Phthalic Acid Ester Derivative Isolated from the Bangladeshi Mangrove Fern Acrostichum aureum

“…The synthetic pharmaceutical excipient CAP was also investigated due to its previously reported antiviral activities [16,17,27]. The cytotoxicity of both compoundswas established against monkey kidney cells (Vero and LLC-MK2).…”

“…Moreover, some phthalates, such as bis(2-methylheptyl) phthalate isolated from the medicinal plant Pongamiapinnata and a fraction from the root bark extract of the guava tree Psidiumguajava, which contains diethyl phthalate and phthalic acid, displayed antiviral activity against White Spot Syndrome Virus [14,15]. Another phthalate, cellulose acetate phthalate (CAP), which is commonly used as a pharmaceutical excipient for the enteric coating of tablets and capsules, has been shown to inactivate herpes simplex virus types 1 and 2 (HSV-1 and 2) and cytomegalovirus in vitro [16], as well as HSV-2 in vivo [16,17].…”