A Thermoresponsive injectable drug delivery system of chitosan/ß-glycerophosphate with gellan gum/alginate microparticles.

The development of new Drug Delivery Systems (DDS) by incorporating microparticles within hydrogels can prolong the release rate of drugs and/or other bioactive agents. In this study, we combined gellan gum/alginate microparticles within a thermoresponsive chitosan (Ch) hydrogel with ß-Glycerophosphate (ß-GP), designing the system to be in the sol state at 21 °C and in the gel state at 37 °C to enable the injectability of the system. The system was in the sol state between 10 °C and 21 °C. Higher concentrations of ß-GP (0, 2, 3, 4, 5 w/v%) and microparticles (0, 2 and 5 w/v%) allowed a faster sol-gel transition with higher mechanical strength at 37 °C. However, the sol-gel transition was not instantaneous. The release profile of methylene blue (MB) from the microparticles was significantly affected by their incorporation in Ch/ß-GP hydrogels, only allowing the release of 60-70 % of MB for 6 days, while the microparticles alone released all the MB in 48 h. The proposed system did not present cytotoxicity to VERO cell lines as a preliminary assay, with the Ch/ß-GP/GG:Alg having >90 % of cellular viability. The proposed Ch/ß-GP system proved to have a delaying effect on drug release and biocompatible properties, being a promising future DDS.

Scalable Processing of Cyclic Olefin Copolymer (COC) Microfluidic Biochips.

Microfluidics evolved with the appearance of polydimethylsiloxane (PDMS), an elastomer with a short processing time and the possibility for replication on a micrometric scale. Despite the many advantages of PDMS, there are well-known drawbacks, such as the hydrophobic surface, the absorption of small molecules, the low stiffness, relatively high cost, and the difficulty of scaling up the fabrication process for industrial production, creating a need for alternative materials. One option is the use of stiffer thermoplastics, such as the cyclic olefin copolymer (COC), which can be mass produced, have lower cost and possess excellent properties. In this work, a method to fabricate COC microfluidic structures was developed. The work was divided into process optimization and evaluation of material properties for application in microfluidics. In the processing step, moulding, sealing, and liquid handling aspects were developed and optimized. The resulting COC devices were evaluated from the point of view of molecular diffusion, burst pressure, temperature resistance, and susceptibility to surface treatments and these results were compared to PDMS devices. Lastly, a target DNA hybridization assay was performed showing the potential of the COC-based microfluidic device to be used in biosensing and Lab-on-a-Chip applications.

Assessing the Genotoxicity of Cellulose Nanomaterials in a Co-Culture of Human Lung Epithelial Cells and Monocyte-Derived Macrophages.

Cellulose micro/nanomaterials (CMNMs) are innovative materials with a wide spectrum of industrial and biomedical applications. Although cellulose has been recognized as a safe material, the unique properties of its nanosized forms have raised concerns about their safety for human health. Genotoxicity is an endpoint that must be assessed to ensure that no carcinogenic risks are associated with exposure to nanomaterials. In this study, we evaluated the genotoxicity of two types of cellulose micro/nanofibrils (CMF and CNF) and one sample of cellulose nanocrystals (CNC), obtained from industrial bleached Eucalyptus globulus kraft pulp. For that, we exposed co-cultures of human alveolar epithelial A549 cells and THP-1 monocyte-derived macrophages to a concentration range of each CMNM and used the micronucleus (MN) and comet assays. Our results showed that only the lowest concentrations of the CMF sample were able to induce DNA strand breaks (FPG-comet assay). However, none of the three CMNMs produced significant chromosomal alterations (MN assay). These findings, together with results from previous in vitro studies using monocultures of A549 cells, indicate that the tested CNF and CNC are not genotoxic under the conditions tested, while the CMF display a low genotoxic potential.

Analysis of the In Vitro Toxicity of Nanocelluloses in Human Lung Cells as Compared to Multi-Walled Carbon Nanotubes.

Cellulose micro/nanomaterials (CMNM), comprising cellulose microfibrils (CMF), nanofibrils (CNF), and nanocrystals (CNC), are being recognized as promising bio-nanomaterials due to their natural and renewable source, attractive properties, and potential for applications with industrial and economical value. Thus, it is crucial to investigate their potential toxicity before starting their production at a larger scale. The present study aimed at evaluating the cell internalization and in vitro cytotoxicity and genotoxicity of CMNM as compared to two multi-walled carbon nanotubes (MWCNT), NM-401 and NM-402, in A549 cells. The exposure to all studied NM, with the exception of CNC, resulted in evident cellular uptake, as analyzed by transmission electron microscopy. However, none of the CMNM induced cytotoxic effects, in contrast to the cytotoxicity observed for the MWCNT. Furthermore, no genotoxicity was observed for CNF, CNC, and NM-402 (cytokinesis-block micronucleus assay), while CMF and NM-401 were able to significantly raise micronucleus frequency. Only NM-402 was able to induce ROS formation, although it did not induce micronuclei. Thus, it is unlikely that the observed CMF and NM-401 genotoxicity is mediated by oxidative DNA damage. More studies targeting other genotoxicity endpoints and cellular and molecular events are underway to allow for a more comprehensive safety assessment of these nanocelluloses.

Cellulose Nanocrystal Aqueous Colloidal Suspensions: Evidence of Density Inversion at the Isotropic-Liquid Crystal Phase Transition.

The colloidal suspensions of aqueous cellulose nanocrystals (CNCs) are known to form liquid crystalline (LC) systems above certain critical concentrations. From an isotropic phase, tactoid formation, growth, and sedimentation have been determined as the genesis of a high-density cholesteric phase, which, after drying, originates solid iridescent films. Herein, the coexistence of a liquid crystal upper phase and an isotropic bottom phase in CNC aqueous suspensions at the isotropic-nematic phase separation is reported. Furthermore, isotropic spindle-like domains are observed in the low-density LC phase and high-density LC phases are also prepared. The CNCs isolated from the low- and high-density LC phases are found to have similar average lengths, diameters, and surface charges. The existence of an LC low-density phase is explained by the presence of air dissolved in the water present within the CNCs. The air dissolves out when the water solidifies into ice and remains within the CNCs. The self-adjustment of the cellulose chain conformation enables the entrapment of air within the CNCs and CNC buoyancy in aqueous suspensions.

The use of isoxazoline and isoxazole scaffolding in the design of novel thiourea and amide liquid-crystalline compounds.

A series of novel thiourea and amide liquid crystals containing 5-membered isoxazoline and isoxazole rings were synthetized and the liquid crystal properties studied. Thioureas were obtained using a condensation reaction of benzoyl chlorides, arylamines and ammonium thiocyanate. The amides, on the other hand, were the byproduct of a quantitative reaction which used potassium cyanate as the starting material. Thiourea and amide derivatives were predominantly SmA mesophase inductors. A nematic mesophase was observed only for thioureas and amides containing an isoxazole ring. Additionaly, the liquid crystal behavior was also dependent on the relative position of nitrogen and oxygen atoms on the 5-membered heterocycle.

Radiographic study of ossification of the pterygospinous and pterygoalar ligaments by the Hirtz axial technique.

The correct radiographic identification of ossification of the pterygospinous and pterygoalar ligaments plays an important role in surgical procedures for the treatment of trigeminal neuralgia. Most of these procedures are performed through the foramen ovale, a site where these ligaments can be found to be partially or completely ossified. We studied the radiographic features of these ossified ligaments and their location in relation to the foramen ovale by the Hirtz axial technique. For this purpose, 93 dry skulls from the Discipline of Anatomy, São José dos Campos Dental School, UNESP, which presented partial or complete ossification of these ligaments, were radiographed. The pterygospinous ligament was detected on 27.97% of radiographs and was partially ossified in 19.36% of cases and completely ossified in 8.61%. The pterygoalar ligament was present in 62.35% of radiographs, being partially ossified in 49.44% and completely ossified in 12.91%. The pterygospinous ligaments was found to be partially and completely ossified on the same radiograph in 3.23% of cases, whereas the pterygoalar ligament appeared partially and completely ossified on the same radiograph in 6.45%. Furthermore, the pterygospinous ligament was thinner than the pterygoalar ligament and located more medially in relation to the foramen ovale. The pterygoalar ligament formed a large bone bar lateral to the foramen ovale, often obliterating the lumen of the latter. The Hirtz axial technique is an excellent tool for the observation of complete or partial ossification of the pterygospinous and pterygoalar ligaments in surgical procedures for the treatment of trigeminal neuralgia performed through the foramen ovale.

Radiographic study of ossification of the pterygospinous and pterygoalar ligaments by the hirtz axial technique

The correct radiographic identification of ossification of the pterygospinous and pterygoalar ligaments plays an important role in surgical procedures for the treatment of trigeminal neuralgia. Most of these procedures are performed through the foramen ovale, a site where these ligaments can be found to be partially or completely ossified. We studied the radiographic features of these ossified ligaments and their location in relation to the foramen ovale by the Hirtz axial technique. For this purpose, 93 dry skulls from the Discipline of Anatomy, Sao Jose dos Campos Dental School, UNESP, which presented partial or complete ossification of these ligaments, were radiographed. The pterygospinous ligament was detected on 27.97% of radiographs and was partially ossified in 19.36% of cases and completely ossified in 8.61%. The pterygoalar ligament was present in 62.35% of radiographs, being partially ossified in 49.44% and completely ossified in 12.91%. The pterygospinous ligaments was found to be partially and completely ossified on the same radiograph in 3.23% of cases, whereas the pterygoalar ligament appeared partially and completely ossified on the same radiograph in 6.45%. Furthermore, the pterygospinous ligament was thinner than the pterygoalar ligament and located more medially in relation to the foramen ovale. The pterygoalar ligament formed a large bone bar lateral to the foramen ovale, often obliterating the lumen of the latter. The Hirtz axial technique is an excellent tool for the observation of complete or partial ossification of the pterygospinous and pterygoalar ligaments in surgical procedures for the treatment of trigeminal neuralgia performed through the foramen ovale.

A correta identificacao radiografica da ossificacao dos ligamentos pterigoespinhoso e pterigoalar e de grande importancia nos procedimentos cirurgicos no tratamento da nevralgia trigeminal. A maioria desses procedimentos e feita via forame oval, local onde podemos encontrar esses ligamentos ossificados, parcial ou totalmente. Estudamos, pela tecnica axial de Hirtz, as caracteristicas radiograficas desses ligamentos ossificados e sua localizacao em relacao ao forame oval. Para isso foram radiografados 93 cranios secos, pertencentes a Disciplina de Anatomia da Faculdade de Odontologia de Sao Jose dos Campos - UNESP, que apresentavam a ossificacao parcial ou total dos referidos ligamentos. Encontramos o ligamento pterigoespinhoso em 27,97% das radiografias, sendo parcialmente ossificado em 19,36% e totalmente em 8,61%. O ligamento pterigoalar estava presente em 62,35% das radiografias, estando parcialmente ossificado em 49,44% e totalmente em 12,91%. O ligamento pterigoespinhoso foi encontrado parcial e totalmente ossificado, numa mesma radiografia, em 3,23% dos casos, enquanto o ligamento pterigoalar apareceu parcial e totalmente ossificado, na mesma radiografia, em 6,45% dos casos. Observamos ainda que o ligamento pterigoespinhoso era menos espesso, em relacao ao ligamento pterigoalar, e localizado mais para medial, em relacao ao forame oval, enquanto que o ligamento pterigoalar formava uma larga barra ossea lateralmente ao forame oval, obliterando muitas vezes o lumen do mesmo. A tecnica axial de Hirtz e um excelente meio para a observacao da ossificacao total ou parcial destes ligamentos, quando de procedimentos cirurgicos que utilizam o forame oval para o tratamento da nevralgia trigeminal.