In an attempt to overcome existing limitations of experimental bone cements we here demonstrate a... more In an attempt to overcome existing limitations of experimental bone cements we here demonstrate a simple approach to synthesizing strontium-modified titania nanotubes (n-SrO-TiO(2) tubes) and functionalize them using the bifunctional monomer methacrylic acid. Then, using 'grafting from' polymerization with methyl methacrylate, experimental bone cements were produced with excellent mechanical properties, radiopacity and biocompatibility. Transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy-dispersive spectroscopy mapping and backscattered SEM micrographs revealed a uniform distribution of SrO throughout the titanium matrix, with retention of the nanotubular morphology. Nanocomposites were then reinforced with 1, 2, 4 and 6 wt.% of the functionalized metal oxide nanotubes. Under the mixing and dispersion regime employed in this study, 2 wt.% appeared optimal, exhibiting a more uniform dispersion and stronger adhesion of the nanotubes in the poly(methyl methacrylate) matrix, as shown by TEM and SEM. Moreover, this optimum loading provided a significant increase in the fracture toughness (K(IC)) (20%) and flexural strength (40%) in comparison with the control matrix (unfilled) at P<0.05. Examination of the fracture surfaces by SEM showed that toughening was provided by the nanotubes interlocking with the acrylic matrix and crack bridging during fracture. On modifying the n-TiO(2) tubes with strontium oxide the nanocomposites exhibited a similar radiopacity to a commercial bone cement (CMW 1), while exhibiting a significant enhancement of osteoblast cell proliferation (242%) in vitro compared with the control at P<0.05.
Neste trabalho foi investigada a incorporacao de argila no tratamento retardante de chama em teci... more Neste trabalho foi investigada a incorporacao de argila no tratamento retardante de chama em tecido de algodao, utilizando bentonita sodica juntamente com aditivos fosfatados, a fim de conferir retardância a chama no substrato textil. Estes componentes foram adicionados a uma dispersao polimerica de EVA e aplicados no tecido usando o metodo de “coating”. A aplicacao do recobrimento retardante de chama nas amostras de tecido resultou na extincao do fogo antes da remocao da fonte de ignicao, em funcao da quantidade de retardante a chama e de argila. O uso da betonita sodica conferiu retardância a chama ao substrato textil gracas ao efeito sinergico entre esta e os aditivos fosfatados. A camada de recobrimento atuou como uma barreira protetora no tecido, tornando a degradacao termica do algodao lenta e gradual. A analise termogravimetrica mostrou uma queda na estabilidade termica das amostras contendo os retardantes a chama, alem da formacao de um residuo carbonoso a 700 °C. As analises de DRX e MET mostraram que a estrutura formada pela argila e a matriz polimerica esta na fronteira entre composito e nanocomposito. O tratamento proposto e eficiente e os tecidos foram classificados como auto-extinguiveis pela norma ISO 6941.
Superparamagnetic iron oxide nanoparticles (SPIONs) have their use approved for the diagnosis/tre... more Superparamagnetic iron oxide nanoparticles (SPIONs) have their use approved for the diagnosis/treatment of malignant tumors and can be metabolized by the organism. To prevent embolism caused by these nanoparticles, they need to be coated with biocompatible and non-cytotoxic materials. Here, we synthesized an unsaturated and biocompatible copolyester, poly (globalide-co-ε-caprolactone) (PGlCL), and modified it with the amino acid cysteine (Cys) via a thiol-ene reaction (PGlCLCys). The Cys-modified copolymer presented reduced crystallinity and increased hydrophilicity in comparison to PGlCL, thus being used for the coating of SPIONS (SPION@PGlCLCys). Additionally, cysteine pendant groups at the particle’s surface allowed the direct conjugation of (bio)molecules that establish specific interactions with tumor cells (MDA-MB 231). The conjugation of either folic acid (FA) or the anti-cancer drug methotrexate (MTX) was carried out directly on the amine groups of cysteine molecules present...
Researchers have concentrated efforts in the search for natural-based reversible inhibitors for c... more Researchers have concentrated efforts in the search for natural-based reversible inhibitors for cholinesterase enzymes because they may play a key role in the treatment and cure of degenerative diseases like Alzheimer’s Disease. Diverse alkaloids from plants can inhibit the action of acetylcholinesterase enzyme and, among them, berberine is a promising bioactive. Although the mechanism of action of berberine still needs to be fully elucidated, the major concern lies in its poor water solubility and consequent low bioavailability. The solid dispersion technique is a well-known procedure to improve the water affinity of hydrophobic substances, however, the obtention of berberine solid dispersions is yet to be truly investigated. It is also of key importance to elucidate the safety aspects of the berberine-loaded solid dispersions and a range of tests can be applied, such as in vitro cytotoxicity in cell lines and in vivo tests using model organisms. In this work, berberine-loaded soli...
The functionalisation of polymacrolactones with phosphoesters was achieved by thiol–ene coupling ... more The functionalisation of polymacrolactones with phosphoesters was achieved by thiol–ene coupling resulting in copolymers with modulated properties.
Nanoencapsulation is a promising approach to protect the volatile compounds in natural lipid mixt... more Nanoencapsulation is a promising approach to protect the volatile compounds in natural lipid mixtures like roasted coffee oil. In this work, nanocapsules were obtained by the miniemulsification-solvent evaporation technique using poly (L-lactic acid) (PLLA) and poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) as encapsulant polymers. The total amount of effectively encapsulated oil was evaluated using a combination of full factorial experimental design and the simplex optimization algorithm and the following independent factors were evaluated: encapsulant polymer, dispersion mechanism, polymer:oil mass ratio and surfactant. The total oil content (oil recovery) was significantly influenced (p<0.05) by two-way and three-way interactions confirming that a complex dependence between the factors took place. If PLLA was the encapsulant polymer, then sonication yielded the highest oil recovery. For PHBV as encapsulant, high shear homogenization (Ultraturrax) led to the highest oil recove...
Exogenous progesterone has several applications in human health and in veterinary medicine, espec... more Exogenous progesterone has several applications in human health and in veterinary medicine, especially in fixed-time artificial insemination protocol. Progesterone nanoencapsulation in biocompatible polymers, such as poly(methyl methacrylate) (PMMA), is an alternative to substitute silicone-based release device traditionally used for estrus control. Progesterone concentration inside the nanoparticles must be precisely known; for that reason, a validation methodology must be applied to ensure reliable results, suitable for nanoparticles application. In this work, an UV-Vis spectrophotometric method was validated for the determination of progesterone in PMMA nanoparticles synthesized by miniemulsion polymerization. Chloroform was used as solvent, showing selectivity to the encapsulated drug and the components of the polymeric matrix did not influence progesterone recovery. Detection and quantitation limits (DL and QL) obtained were 0.32 and 0.96 mg·L−1, respectively, and precision tes...
Journal of materials science. Materials in medicine, 2016
Lauryl gallate loaded in superparamagnetic poly(methyl methacrylate) nanoparticles surface modifi... more Lauryl gallate loaded in superparamagnetic poly(methyl methacrylate) nanoparticles surface modified with folic acid were synthesized by miniemulsion polymerization in just one step. In vitro biocompatibility and cytotoxicity assays on L929 (murine fibroblast), human red blood, and HeLa (uterine colon cancer) cells were performed. The effect of folic acid at the nanoparticles surface was evaluated through cellular uptake assays in HeLa cells. Results showed that the presence of folic acid did not affect substantially the polymer particle size (~120 nm), the superparamagnetic behavior, the encapsulation efficiency of lauryl gallate (~87 %), the Zeta potential (~38 mV) of the polymeric nanoparticles or the release profile of lauryl gallate. The release profile of lauryl gallate from superparamagnetic poly(methyl methacrylate) nanoparticles presented an initial burst effect (0-1 h) followed by a slow and sustained release, indicating a biphasic release system. Lauryl gallate loaded in s...
The encapsulation of superparamagnetic nanoparticles (MNPs) in polymeric nanoparticles (NPs) with... more The encapsulation of superparamagnetic nanoparticles (MNPs) in polymeric nanoparticles (NPs) with modified surfaces can improve targeted delivery and induce cell death by hyperthermia. The goals of this study were to synthesize and characterize surface modified superparamagnetic poly(methyl methacrylate) with folic acid (FA) prepared by miniemulsion polymerization (MNPsPMMA-FA) and to evaluate their in vitro cytotoxicity and cellular uptake in non-tumor cells, murine fibroblast (L929) cells and tumor cells that overexpressed folate receptor (FR) β, and chronic myeloid leukemia cells in blast crisis (K562). Lastly, hemolysis assays were performed on human red blood cells. MNPsPMMA-FA presented an average mean diameter of 135 nm and a saturation magnetization (Ms) value of 37 emu/g of iron oxide, as well as superparamagnetic behavior. The MNPsPMMA-FA did not present cytotoxicity in L929 and K562 cells. Cellular uptake assays showed a higher uptake of MNPsPMMA-FA than MNPsPMMA in K562 cells when incubated at 37 °C. On the other hand, MNPsPMMA-FA showed a low uptake when endocytosis mechanisms were blocked at low temperature (4 °C), suggesting that the MNPsPMMA-FA uptake was mediated by endocytosis. High concentrations of MNPsPMMA-FA showed hemocompatibility when incubated for 24 h in human red blood cells. Therefore, our results suggest that these carrier systems can be an excellent alternative in targeted drug delivery via FR.
In an attempt to overcome existing limitations of experimental bone cements we here demonstrate a... more In an attempt to overcome existing limitations of experimental bone cements we here demonstrate a simple approach to synthesizing strontium-modified titania nanotubes (n-SrO-TiO(2) tubes) and functionalize them using the bifunctional monomer methacrylic acid. Then, using &amp;amp;amp;amp;amp;amp;amp;amp;#39;grafting from&amp;amp;amp;amp;amp;amp;amp;amp;#39; polymerization with methyl methacrylate, experimental bone cements were produced with excellent mechanical properties, radiopacity and biocompatibility. Transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy-dispersive spectroscopy mapping and backscattered SEM micrographs revealed a uniform distribution of SrO throughout the titanium matrix, with retention of the nanotubular morphology. Nanocomposites were then reinforced with 1, 2, 4 and 6 wt.% of the functionalized metal oxide nanotubes. Under the mixing and dispersion regime employed in this study, 2 wt.% appeared optimal, exhibiting a more uniform dispersion and stronger adhesion of the nanotubes in the poly(methyl methacrylate) matrix, as shown by TEM and SEM. Moreover, this optimum loading provided a significant increase in the fracture toughness (K(IC)) (20%) and flexural strength (40%) in comparison with the control matrix (unfilled) at P&amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05. Examination of the fracture surfaces by SEM showed that toughening was provided by the nanotubes interlocking with the acrylic matrix and crack bridging during fracture. On modifying the n-TiO(2) tubes with strontium oxide the nanocomposites exhibited a similar radiopacity to a commercial bone cement (CMW 1), while exhibiting a significant enhancement of osteoblast cell proliferation (242%) in vitro compared with the control at P&amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05.
Neste trabalho foi investigada a incorporacao de argila no tratamento retardante de chama em teci... more Neste trabalho foi investigada a incorporacao de argila no tratamento retardante de chama em tecido de algodao, utilizando bentonita sodica juntamente com aditivos fosfatados, a fim de conferir retardância a chama no substrato textil. Estes componentes foram adicionados a uma dispersao polimerica de EVA e aplicados no tecido usando o metodo de “coating”. A aplicacao do recobrimento retardante de chama nas amostras de tecido resultou na extincao do fogo antes da remocao da fonte de ignicao, em funcao da quantidade de retardante a chama e de argila. O uso da betonita sodica conferiu retardância a chama ao substrato textil gracas ao efeito sinergico entre esta e os aditivos fosfatados. A camada de recobrimento atuou como uma barreira protetora no tecido, tornando a degradacao termica do algodao lenta e gradual. A analise termogravimetrica mostrou uma queda na estabilidade termica das amostras contendo os retardantes a chama, alem da formacao de um residuo carbonoso a 700 °C. As analises de DRX e MET mostraram que a estrutura formada pela argila e a matriz polimerica esta na fronteira entre composito e nanocomposito. O tratamento proposto e eficiente e os tecidos foram classificados como auto-extinguiveis pela norma ISO 6941.
Superparamagnetic iron oxide nanoparticles (SPIONs) have their use approved for the diagnosis/tre... more Superparamagnetic iron oxide nanoparticles (SPIONs) have their use approved for the diagnosis/treatment of malignant tumors and can be metabolized by the organism. To prevent embolism caused by these nanoparticles, they need to be coated with biocompatible and non-cytotoxic materials. Here, we synthesized an unsaturated and biocompatible copolyester, poly (globalide-co-ε-caprolactone) (PGlCL), and modified it with the amino acid cysteine (Cys) via a thiol-ene reaction (PGlCLCys). The Cys-modified copolymer presented reduced crystallinity and increased hydrophilicity in comparison to PGlCL, thus being used for the coating of SPIONS (SPION@PGlCLCys). Additionally, cysteine pendant groups at the particle’s surface allowed the direct conjugation of (bio)molecules that establish specific interactions with tumor cells (MDA-MB 231). The conjugation of either folic acid (FA) or the anti-cancer drug methotrexate (MTX) was carried out directly on the amine groups of cysteine molecules present...
Researchers have concentrated efforts in the search for natural-based reversible inhibitors for c... more Researchers have concentrated efforts in the search for natural-based reversible inhibitors for cholinesterase enzymes because they may play a key role in the treatment and cure of degenerative diseases like Alzheimer’s Disease. Diverse alkaloids from plants can inhibit the action of acetylcholinesterase enzyme and, among them, berberine is a promising bioactive. Although the mechanism of action of berberine still needs to be fully elucidated, the major concern lies in its poor water solubility and consequent low bioavailability. The solid dispersion technique is a well-known procedure to improve the water affinity of hydrophobic substances, however, the obtention of berberine solid dispersions is yet to be truly investigated. It is also of key importance to elucidate the safety aspects of the berberine-loaded solid dispersions and a range of tests can be applied, such as in vitro cytotoxicity in cell lines and in vivo tests using model organisms. In this work, berberine-loaded soli...
The functionalisation of polymacrolactones with phosphoesters was achieved by thiol–ene coupling ... more The functionalisation of polymacrolactones with phosphoesters was achieved by thiol–ene coupling resulting in copolymers with modulated properties.
Nanoencapsulation is a promising approach to protect the volatile compounds in natural lipid mixt... more Nanoencapsulation is a promising approach to protect the volatile compounds in natural lipid mixtures like roasted coffee oil. In this work, nanocapsules were obtained by the miniemulsification-solvent evaporation technique using poly (L-lactic acid) (PLLA) and poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) as encapsulant polymers. The total amount of effectively encapsulated oil was evaluated using a combination of full factorial experimental design and the simplex optimization algorithm and the following independent factors were evaluated: encapsulant polymer, dispersion mechanism, polymer:oil mass ratio and surfactant. The total oil content (oil recovery) was significantly influenced (p<0.05) by two-way and three-way interactions confirming that a complex dependence between the factors took place. If PLLA was the encapsulant polymer, then sonication yielded the highest oil recovery. For PHBV as encapsulant, high shear homogenization (Ultraturrax) led to the highest oil recove...
Exogenous progesterone has several applications in human health and in veterinary medicine, espec... more Exogenous progesterone has several applications in human health and in veterinary medicine, especially in fixed-time artificial insemination protocol. Progesterone nanoencapsulation in biocompatible polymers, such as poly(methyl methacrylate) (PMMA), is an alternative to substitute silicone-based release device traditionally used for estrus control. Progesterone concentration inside the nanoparticles must be precisely known; for that reason, a validation methodology must be applied to ensure reliable results, suitable for nanoparticles application. In this work, an UV-Vis spectrophotometric method was validated for the determination of progesterone in PMMA nanoparticles synthesized by miniemulsion polymerization. Chloroform was used as solvent, showing selectivity to the encapsulated drug and the components of the polymeric matrix did not influence progesterone recovery. Detection and quantitation limits (DL and QL) obtained were 0.32 and 0.96 mg·L−1, respectively, and precision tes...
Journal of materials science. Materials in medicine, 2016
Lauryl gallate loaded in superparamagnetic poly(methyl methacrylate) nanoparticles surface modifi... more Lauryl gallate loaded in superparamagnetic poly(methyl methacrylate) nanoparticles surface modified with folic acid were synthesized by miniemulsion polymerization in just one step. In vitro biocompatibility and cytotoxicity assays on L929 (murine fibroblast), human red blood, and HeLa (uterine colon cancer) cells were performed. The effect of folic acid at the nanoparticles surface was evaluated through cellular uptake assays in HeLa cells. Results showed that the presence of folic acid did not affect substantially the polymer particle size (~120 nm), the superparamagnetic behavior, the encapsulation efficiency of lauryl gallate (~87 %), the Zeta potential (~38 mV) of the polymeric nanoparticles or the release profile of lauryl gallate. The release profile of lauryl gallate from superparamagnetic poly(methyl methacrylate) nanoparticles presented an initial burst effect (0-1 h) followed by a slow and sustained release, indicating a biphasic release system. Lauryl gallate loaded in s...
The encapsulation of superparamagnetic nanoparticles (MNPs) in polymeric nanoparticles (NPs) with... more The encapsulation of superparamagnetic nanoparticles (MNPs) in polymeric nanoparticles (NPs) with modified surfaces can improve targeted delivery and induce cell death by hyperthermia. The goals of this study were to synthesize and characterize surface modified superparamagnetic poly(methyl methacrylate) with folic acid (FA) prepared by miniemulsion polymerization (MNPsPMMA-FA) and to evaluate their in vitro cytotoxicity and cellular uptake in non-tumor cells, murine fibroblast (L929) cells and tumor cells that overexpressed folate receptor (FR) β, and chronic myeloid leukemia cells in blast crisis (K562). Lastly, hemolysis assays were performed on human red blood cells. MNPsPMMA-FA presented an average mean diameter of 135 nm and a saturation magnetization (Ms) value of 37 emu/g of iron oxide, as well as superparamagnetic behavior. The MNPsPMMA-FA did not present cytotoxicity in L929 and K562 cells. Cellular uptake assays showed a higher uptake of MNPsPMMA-FA than MNPsPMMA in K562 cells when incubated at 37 °C. On the other hand, MNPsPMMA-FA showed a low uptake when endocytosis mechanisms were blocked at low temperature (4 °C), suggesting that the MNPsPMMA-FA uptake was mediated by endocytosis. High concentrations of MNPsPMMA-FA showed hemocompatibility when incubated for 24 h in human red blood cells. Therefore, our results suggest that these carrier systems can be an excellent alternative in targeted drug delivery via FR.
Uploads