Design of a "microbicide" for prevention of sexually transmitted diseases using "inactive" pharmaceutical excipients.
The human immunodeficiency virus (HIV-1) pandemic has been driven primarily by the sexual transmission of the virus, and facilitated by prior infections with other sexually transmitted disease (STD) pathogens. Although treatment of these STDs has been proposed as a means to decrease the rate of HIV-1 sexual transmission, preventive measures effective against both HIV-1 and other STD pathogens are expected to have a larger impact. These measures include topically applied mechanical and chemical (i.e. microbicidal) barriers. Microbicides of preference should have a broad specificity against diverse STD pathogens and a well established safety record, considering their repeated use over decades. Here, we report that cellulose acetate phthalate (CAP), an "inactive" pharmaceutical excipient, commonly used in the production of enteric tablets and capsules: (1) has antiviral activity against HIV-1 and several herpesviruses (HSV); and (2) when appropriately formulated, in micronized form, inactivates HIV-1, HSV-1, HSV-2, cytomegalovirus, Neisseria gonorrhoeae, Trichomonas vaginalis, Haemophilus ducreyi and Chlamydia trachomatis but does not affect Lactobacilli, components of the natural vaginal flora contributing to resistance against STDs. Thus, the CAP formulations meet the criteria for preferred microbicides and warrant further evaluation in vivo in humans.
Neurath
A R
AR
The New York Blood Center, 310 E. 67th St, New York, NY, 10021, USA.
Strick
N
N
Li
Y Y
YY
Lin
K
K
Jiang
S
S
D000818:Animals; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002460:Cell Line; D002482:Cellulose / Q000031:analogs & derivatives* / Q000494:pharmacology; D002692:Chlamydia trachomatis / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005079:Excipients / Q000494:pharmacology*; D015658:HIV Infections / Q000517:prevention & control; D015497:HIV-1 / Q000187:drug effects; D006191:Haemophilus ducreyi / Q000187:drug effects; D018259:Herpesvirus 1, Human / Q000187:drug effects; D018258:Herpesvirus 2, Human / Q000187:drug effects; D006801:Humans; D007778:Lactobacillus / Q000187:drug effects; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009344:Neisseria gonorrhoeae / Q000187:drug effects; D012749:Sexually Transmitted Diseases / Q000517:prevention & control*; D014246:Trichomonas vaginalis / Q000187:drug effects
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D005079:Excipients; D002482:Cellulose; C011708:cellulose acetate phthalate; D008747:Methylcellulose; C053309:hydroxypropyl methylcellulose phthalate