A new method of contraception
A contraceptive gel based on chitosan strengthens the mucous barrier of the cervix
Tatiana Sashina, PCR.news
Affordable contraceptives have made pregnancy planning possible, which has a beneficial effect on the health of mothers and their children, and at the global level contributes to solving the problems of gender inequality, poverty and hunger. However, about 40% of pregnancies worldwide are still unplanned. Hormonal contraception is highly effective, however, due to the risk of side effects, a significant part of users stop using them or prefer non-hormonal drugs, which also have their drawbacks. For example, the use of copper intrauterine devices (IUDs) is interrupted in about 20% of cases due to their displacement or pain. Condoms and spermicides are less invasive than IUDs, but less effective than hormonal methods. Thus, there is a clear need for contraceptives with alternative mechanisms of action.
A group of researchers from Sweden, Denmark and France has developed a method to strengthen the cervical mucosal barrier during ovulation using chitosan, which can potentially be used for contraception. Chitosan, a biopolymer consisting of β-(1-4)-D-glucosamine units and N-acetyl-D-glucosamine, is widely used for biomedical purposes, including because of its mucoadhesive properties. Previously, scientists have already shown that chitosan polysaccharides can cross-link mucin gel in the stomach of pigs, enhancing its barrier properties. In the new work, they proposed a similar non—hormonal approach - physical cross-linking of the mucin network of the cervical barrier with chitosan to block the passage of sperm through it.
In the new work, the scientists used chitosan obtained by deacetylation of chitin isolated from the cell wall of fungi or the shell of crustaceans. They first conducted an in vitro study in which they used biomaterial obtained from humans. Chitosans with a molecular weight of more than 7 kDa passively diffused into the ovulatory cervical mucus, effectively stitched it and prevented the penetration of spermatozoa. This helped to select candidate molecules for further in vivo testing.
To demonstrate the blocking ability of chitosan, scientists used Ile-de-France sheep. They developed a chitosan-based gel with a molecular weight of 36.2 kDa and tested it on sheep before artificial insemination. The use of sheep made it possible to visualize fluorescently labeled spermatozoa in the vagina and their progress up the genital tract. All experiments on sheep were carried out on the day of ovulation. At least seven animals were used to count spermatozoa. The researchers demonstrated that chitosan-containing vaginal gels stopped sheep sperm at the entrance to the cervical canal and prevented them from entering the uterus. On average, the gel resulted in a 98% decrease in the number of spermatozoa in the uterus compared to control animals receiving the same gel, but without chitosan. For comparison, the effectiveness of birth control pills ranges from 91 to 99%.
Also, using a sheep model, scientists assessed the toxicity of the chitosan preparations obtained. Unlike the spermicide nonoxynol-9, chitosan preparations did not damage or irritate the vaginal epithelium of sheep. These toxicological data were supplemented with in vitro analyses, in which the researchers tested the effect of the composition containing chitosan on the speed, movement pattern and viability of sperm. Chitosan did not affect sperm motility in vitro or in vivo, which proved the strengthening of the physical mucus barrier as the main mechanism of action of the new contraceptive, which distinguishes it from spermicides that kill sperm.
Thus, this work can become the basis for the development of a new type of contraceptives. One of the authors, Thomas Cruzier, a biopolymer researcher from the Royal Institute of Technology (Stockholm, Sweden), founded the company Cirqle Biomedical to conduct further research and clinical trials. Cirqle Biomedical has entered into a $360 million partnership agreement with Organon, a women's health company, to develop and promote the technology. As Kruzier explains, the new product can be used from a few seconds to several hours before sexual intercourse, and its effect can last for hours, but decreases with time, as the mucous barrier is replaced naturally.
Article by Schimpf et al. Topical reinforcement of the cervical mucus barrier to sperm is published in the journal Science Translational Medicine.
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