ABSTRACT Introduction: n-Butyl cyanoacrylate (BCA) and its polymer, poly (n-butyl cyanoacrylate) (PBCA) have excellent adhesive, biocompatible and biodegradable properties for medical applications. The current work presents new methods for producing BCA of high purity and PBCA micro/nanofibers as potencial pharmaceutic products. Methods: Microwave radiation was used for producing BCA, and electro-spinning technique for PBCA micro/nanofibers, whose physical chemistry, mechanical, biological and drug delivery properties were evaluated. Results: The process time for BCA production was reduced by a factor from 3 to 5 fold when microwave radiation was used respecting oil bath. The application of electro-spinning to solutions of PBCA with different molecular weights produced fibers free of defects with diameters between 400 nm and 5 μm. Young´s modulus and maximal tension values were determined in the range from 0,7 MPa to 1,9 MPa and 0,05 MPa to 0,12 MPa respectively. The thermal degradation of PBCA nanofibers and those charged with 15% of 5-fluorouracil was 110 oC to 241oC and 100 oC to 309 oC, with the corresponding maximal peaks at 186 oC and 203 oC. The cytostatic 5-fluorouracil was homogeneously loaded inside PBCA fibers, with a release of 20 % in 7 days and the rest gradually (until 96 days) in physiological medium. Human fibroblasts proliferated over PBCA nanofibers. As a conclusion: Microwave radiation reduces the reaction time for BCA synthesis in a significant way. The electro-spinning of PBCA produces meshes based on micro/nanofibers, which can be used as drug delivery and tissue engineering systems.

RESUMEN Introducción: El cianoacrilato de n-butilo (BCA) y su polímero, el policianoacrilato de n-butilo (PBCA) poseen excelentes propiedades adhesivas, biocompatibles y biodegradables para aplicaciones médicas. Este trabajo presenta nuevos métodos para producir BCA de alta pureza y micro/nanofibras de PBCA como potenciales productos farmacéuticos. Métodos: La radiación de microondas se utilizó para producir BCA y la técnica de electro-hilado para las micro/nanofibras de PBCA, cuyas propiedades química-físicas, mecánicas, biológicas y de transportación de fármacos fueron evaluadas. Resultados: El tiempo del proceso para la producción del BCA se redujo de 3 veces a 5 veces al emplear la radiación de microondas respecto al baño de aceite. El electro-hilado a disoluciones de PBCA con distintas masas moleculares produjo fibras libres de defectos con diámetros de 400 nm a 5 μm. Se determinaron valores del módulo de Young y de tensión máxima de 0,7 MPa a 1,9 MPa y de 0,05 MPa a 0,12 MPa respectivamente. La degradación térmica de las nanofibras de PBCA y las cargadas con 15 % de 5-fluorouracilo ocurrió de 110 oC a 241 oC y de 100 oC a 309 oC con sus respectivos máximos en 186 oC y 203 oC. El citostático 5-fluorouracilo se distribuyó homogéneamente en las fibras de PBCA, liberándose el 20 % en 7 días y el resto de forma gradual (hasta 96 días) en medio fisiológico. Los fibroblastos humanos proliferaron sobre las nanofibras de PBCA. Como conclusiones, la radiación de microondas reduce significativamente el tiempo de síntesis del BCA. El electro-hilado del PBCA produce mallas constituidas por micro/nanofibras, que pudieran utilizarse como sistemas transportadores de fármacos y para ingeniería de tejidos.

In this study mechanical properties and biocompatibility (In Vitro) of a new bone cement were investigated. A new platform technology named COOL is a variable composite of dissolved, chemically modified PMMA and different bioceramics. COOL cures at body temperature via a classical cementation reaction. Compressive strengths ranging from 3.6 ± 0.8 to 62.8 ± 1.3 MPa and bending strengths ranging from 9.9 ± 2.4 to 26.4 ± 3.0 MPa were achieved with different COOL formulations. Porosity varied between 31 and 43%. Varying the components of each formulation mechanical properties and porosity could be adjusted. In Vitro biocompatibility studies with primary human osteoblasts (pHOB) in direct contact with different COOL formulations, did not reveal any signs of toxicity. In contrast to Refobacin® R, cells incubated with COOL showed similar density, viability and ALP activity compared to control, if specimen were added immediately to the cell monolayer after preparation. In conclusion, COOL has promising mechanical properties in combination with high biocompatibility In Vitro and combines different advantages of both CPCs and PMMA cements by avoiding some of the respective shortcomings.