Emprego de matriz polimérica biodegradável em dispositivos vaginais para liberação sustentada de progesterona em fêmeas bovinas: testes in vitro e in vivo / Use of biodegradable polymeric matrix, in vaginal devices, to sustained progesterone release in cows: in vitro e in vivo tests

AUTOR(ES)
DATA DE PUBLICAÇÃO

2006

RESUMO

With the increase in the number of animals inseminated by TAI (timed artificial insemination) the decrease of costs and the improvement of reproductive performance are the goals of several research groups. Progesterone devices which are majority constituted of a nylon skeleton covered with a silicone layer with P4, are used in TAI protocols. Aiming the decrease of the production costs and the environmental impact, was a new device developed with biopolymers matrix. In this study, were compared a blend of Poli-hidroxi-butirate (PHB) and poli-?-caprolactone (PCL) device with the Bovine Internal Device (DIB®). In the in vitro test, two kinds of the new device with a superficial area of 147 cm2: DISP8 (46% PHB, 46% PCL and 8% P4; n=4), DISP10 (45% PHB, 45% PCL, 10% P4; n=4) and DIB® (1 g of P4, area of 120 cm2; n=3). The in vitro tests were led following USP 23 specifications in a drug dissolutor in alcohol/water (60/40) solution as a diffusion medium. Samples were collected at 2 min., 2, 4, 8, 12, 24, 48, 60, 72, 84 and 96 hours. Progesterone concentrations were estimated by spectrophotometry at UV 244 nm wavelenght. Comparisons 3 by 3 of the angular coefficients of the straight lines obtained by the regression of the accumulated P4 concentrations in function of the square root of time were performed. The averages and respective standard-errors of the angular coefficients were 677,39 ± 16.13 µg/cm2/t1/2 to DIB®, 566,17 ± 3.68 µg/cm2/t1/2 to Disp8 and 774,63 ± 45.26 µg/cm2/t1/2 to Disp10. Difference were observed between DISP8 and DISP10 (p<0.05) but both did not differ to DIB®. Four periods were considered for analysis of the amounts released per day of in vitro test: 0-24, 24-48, 48-72 and 72-96 hours. Interaction between treatment and time was observed (p=0.0024). In the first 24 hours DISP8 released significantly less P4 than DISP10 and DIB® but the lathers did not differ from each other. In the interval between 24 and 48 hours DISP10 released significantly more P4 than DIB®. The device DISP8 released an intermediary concentration of P4 and was similar to DIB® and to DISP10. In the interval between 48 and 72 hours the progesterone concentration released by DISP10 was significantly higher than DIB® and DISP8 but lathers did not differ from each other. In the interval between 72 and 96 hours DISP10 released significantly more P4 than DIB® while DISP8 released an intermediary amount which did not differ to DIB® or to DISP10. In the test in vivo test, six ovariectomized beef cows received the devices DIB® (n=4) or DISP8 (n=8) in an alternated delineation in a nom balanced sequence (cross-over) added of repeated measures in time, related to the 16 days of blood samples collects. Progesterone concentration from these samples were measured by radioimmunoassay in solid phase using the commercial kit from DPC (Diagnostics Products Corporation). The peak of the progesterone concentrations were observed 4 hours after the devices insertion and this was the unique moment in which plasmatic progesterone concentrations differed depending on device (11,45 ± 1,96 vs 9,23 ± 1,15 ng/mL, respectively for DIB and DISP8; p= 0,027). After 8 days from the device insertion plasmatic progesterone concentrations provided by DIB and DISP8 were respectively 2,44 ± 0,09 and 1,89 ± 0,13 ng/mL (p=0.58). Both devices kept the progesterone concentration higher than 1 ng/mL during the 16 days of the in vivo test. In conclusion, the devices made with biopolymers blends of PHB/PCL can release sustained P4 comparable with silicone matrix.

ASSUNTO(S)

phb/ pcl progesterone phb/ pcl biopolímeros device bovine females fêmeas bovinas progesterona dispositivo biopolymers

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