Design and evaluation of a recyclable intravaginal device made of ethylene vinyl acetate copolymer for bovine estrus synchronization

• Published in: Drug delivery and translational research 2020-10, Vol.10 (5), p.1255-1266
• Main Authors: Helbling, Ignacio M., Karp, Federico, Cappadoro, Alejandro, Luna, Julio A.
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Original Article; Pharmaceutical Sciences/Technology
• ISSN: 2190-393X; 2190-3948
• DOI: 10.1007/s13346-020-00717-4

In bovine estrus synchronization, intravaginal devices made of silicone are used to administer exogenous progesterone with the aim of maintain plasmatic levels above 2 ng ml −1 during the treatment. After their use, devices must be discarded. There is an important concern on the environmental impact of the disposal of these used products due mainly to the non-degradability of the silicone and to the residual content of the hormone. Different alternatives are being studied, and the use of ecological materials appears as the more important. The objective of the present contribution was to design and evaluate a recyclable intravaginal prototype using ethylene vinyl acetate copolymer (EVA). Devices were fabricated by an injection-molding technique and characterized in terms of dimensions, loading efficiency, release rate, and wing tension. An analysis was first conducted to compare three different matrices and two supports. Secondly, the best candidate prototype was assayed in both beef and dairy cattle. Finally, used matrices were recycled measuring the progesterone content in the resulting devices and testing them in vitro. According to release tests, no differences were observed between the three matrices both in vitro and in vivo. On the contrary, a better performance was achieved when a support with a more flexible Y shape was used in comparison with a rigid T geometry. Successful results were observed in non-lactating cows, with plasma concentrations above the threshold value defined for the synchronization therapy. However, lower progesterone levels resulted when devices were tested in animals with large milk production. By last, recycled matrices presented a similar initial content and in vitro release rate than original matrices. These findings could open the possibility to use recyclable EVA devices as an alternative to the non-degradable silicone intravaginal inserts. Future research must be carried out to optimize the performance of the recycled matrices in dairy cattle. Modifications of the release surface and/or the initial loading can give a solution to the lower values observed in these animals. Graphical abstract