Spermicidal agents exert an anti-fertility effect upon spermatozoa as they pass through the female reproductive tract. They must act either to kill or immobilize sperm or render them incapable fertilization. These agents may act on a number of sperm functions; therefore, it is important to examine potential spermicidal actions with a battery of physiological, cellular and biochemical assays to secure a clear understanding of contraceptive efficacy. The spermicidal agent, nonoxynol-9, acts on the sperm plasma membrane to result in solubilization and cell death. Cellulose acetate phthalate (CAP) offers promise as a safe and effective broad-spectrum microbicidal agent. While nonoxynol-9 disrupts sperm cellular integrity by its detergent nature, the phthalic acid residues of CAP, essential for its antiviral activity, are expected to exert spermicidal activity by providing low pH buffering and hydrophobicity. The objective of this proposal is to examine its potential spermicidal actions. From the aforementioned observations, the hypothesis is: CAP possesses spermicidal activity and will act to disrupt sperm functions by a number of different physical and biochemical actions.
The specific aims are: (1) determine the effects of soluble CAP at neutral pH on sperm functional capacity; (2) determine the binding potential of soluble CAP at neutral pH to human sperm; (3) characterize the effects of a topical cream containing micronized CAP and a CAP sponge on sperm functional capacity and cervical mucus receptivity; and, test the in vivo contraceptive activity of CAP formulations in a rabbit model. Information gleaned for these studies will provide essential information on the spermicidal activity of CAP formulations. With a clear understanding of the spermicidal actions of CAP, the applicant will have identified a broad-spectrum microbicide with spermicidal activity that acts without detergent-like toxicity which will provide a woman-managed method of contraception and prevention of STD, including HIV-1 transmission.
Showing the most recent 10 out of 25 publications
