Spermicidal activity

Topical spermicides such as nonoxynol-9 (N9) and benzalkonium chloride act on sperm membranes through a detergent effect, namely, hydrophobe-hydrophobe interaction between the active and substrate (spermatozoa). The idea was to optimize the cationic/hydrophobic polymer in the drug delivery system so epithelial cells were protected without sacrificing the drug s spermicidal activity. One of the questions that needed to be answered in designing an optimum cationic/hydrophobe modified polymer was the effect of the hydrophobe on the drug activity (N9 initially, and other actives subsequently). 

A series of DCE-based formulations containing Igepal CO-630 Special (N9) and dextran sulfate (DS) were evaluated for in vitro contraceptive testing. Also included in the screening tests were placebos, N9, two commercial spermicidal products (Conceptrol and KY Plus), vaginal moisturizer products (KY Jelly and Replens ), and saline. Test results are summarized in Table 6. The N9-containing products exhibited similar spermicidal activity, as illustrated by the minimum effective concentration (MEC). Samples without N9 did not have spermicidal activity. DCE placebo vehicle inhibits sperm penetration into the cervical mucus, illustrated by the very low MOET values after 1 10 and 1 160 dilutions. This activity has not been reported for anionic or nonionic polymer vehicles. There are no striking differences... 

A correlation exists for a surfactant s spermicidal activity and partition coefficient, such that the MEC is in the order of nonionic > cationic > anionic for given stmctural variables [47]. Such design parameters need to be factored when designing polymer vehicles and formulations with ionic and hydrophobic features. 

Furuse, K., Ishizeki, C., and Iwahara, S. Studies on spermicidal activity of surfactants. I. Correlation between spermicidal effect and physicochemical properties of p-menthanylphenyl polyoxyethylene (8.8) ether and related surfactants. J. Pharm. Dyn. 1983, 6, 359-372. 

Cesari et al. (2007) demonstrated on bovine and human sperm in vitro that potato aspartic proteases 1 and 3 are effective spermicidal compounds. Spermicidal activity is due to membrane permeabilization and is not related to the proteolytic activity. Cesari et al. (2007) suggest vaginal contraception as a possible applieation. 

A gelly microemulsion loaded with a phenyl phosphate derivative of zidovudine has been developed to prevent the HIV transmission [24]. This new drug also presents a spermicidal activity. The gel formulation is characterized by low cytotoxicity towards human vaginal,... 

Lee, C.H., R. Bagdon, and Y.W. Chien. 1996. Comparative in vitro spermicidal activity and synergistic effect of chelating agents with nonoxynol-9 on human sperm functionality. J Pharm Sci 85 91. 

Also, gel microemulsions have been recently reported as safe and devoid of mucosal toxicity drug delivery systems, presenting intrinsic spermicide activity and the possibility of improving vaginal bioavailability of poorly soluble antimicrobial agents [100],... 

Yu, K. Chien, Y. Spermicidal activity-structure relationship of nonoxynol oligomers physicochemical basis. Int. J. Pharm. 1995, 125, 81-90. 

D cruz, O. Venkatachalam, T. Uckun, F. Structural requirements for potent human spermicidal activity of dual function aryl phosphate derivative of bromo-methoxy zidovudine. Biol Reprod 2000, 62, 37-44. 

When several diterpenoids and triterpenoids, isolated from the herb, were examined for antifertility activity, 1 showed the most potent in vitro spermicidal activity [99]. In contrast, 4 had the most potent male in vivo antifertility effect in the modified MB-50 assay, and it was therefore suggested that 4 might be a good candidate to be developed into a male antifertility agent. 

The saponin fraction of S. officinalis has shown antiinflammatory activity in vitro against carrageenan-induced rat-paw oedema and inhibited prostaglandin synthetase [49]. Purified saponins have been recently shown to possess hypocholesterolaemic effects in vivo, which is believed to be due to the ability of the saponin to form an insoluble complex with cholesterol, preventing its absorption from the small intestine [50]. The saponins also demonstrated spermicidal activity, which may come from their hemolytic property [51]. 

KhUlare, B., and T.G. Shrivastav. 2003. Spermicidal activity of Azadirachta indica (neem) leaf extract. Contraception 68(3) 225-229. Khosla, P, S. Bhanwra, J. Singh, S. Seth, and R.K. Srivastava. 2000. A study of hypoglycaemic effects of Azadirachta indica (Neem) in normal and alloxan diabetic rabbits. Indian J. Physiol. Pharmacol. 44(l) 69-74. 

They have tested metallocenes containing Ti, Zr, Mo, and Hf and found that they did not have spermicidal activity [22], In comparison, a wide range of vanadocene compounds exhibit good spermicidal activity. Some of these compounds are shown in Figure 9,1 in decreasing order of efficacy [22],... 

Figure 9.1 Vanadocene compounds that exhibit spermicidal activity [23]...

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