Spatial rigid-multi-body systems with lubricated spherical clearance joints : modeling and simulation

The dynamic modeling and simulation of spatial rigid-multi-body systems with lubricated spherical joints is the main purpose of the present work. This issue is of paramount importance in the analysis and design of realistic multibody mechanical systems undergoing spatial motion. When the spherical clearance joint is modeled as dry contact; i.e., when there is no lubricant between the mechanical elements which constitute the joint, a body-to-body (typically metal-to-metal) contact takes place. The joint reaction forces in this case are evaluated through a Hertzian-based contact law. A hysteretic damping factor is included in the dry contact force model to account for the energy dissipation during the contact process. The presence of a fluid lubricant avoids the direct metal-to-metal contact. In this situation, the squeeze film action, due to the relative approaching motion between the mechanical joint elements, is considered utilizing the lubrication theory associated with the spherical bearings. In both cases, the intra-joint reaction forces are evaluated as functions of the geometrical, kinematical and physical characteristics of the spherical joint. These forces are then incorporated into a standard formulation of the system’s governing equations of motion as generalized external forces. A spatial four bar mechanism that includes a spherical clearance joint is considered here as example. The computational simulations are carried out with and without the fluid lubricant, and the results are compared with those obtained when the system is modeled with perfect joints only. From the general results it is observed that the system’s performance with lubricant effect presents fewer peaks in the kinematic and dynamic outputs, when compared with those from the dry contact joint model.Fundação para a Ciência e a Tecnologia (FCT

Dexamethasone-loaded poly(epsilon-caprolactone) intravitreal implants: a pilot study.

PURPOSE: Poly(epsilon-caprolactone) (PCL) is a biodegradable and biocompatible polymer that presents a very low degradation rate, making it suitable for the development of long-term drug delivery systems. The objective of this pilot study is to evaluate the feasibility and characteristics of PCL devices in the prolonged and controlled intravitreous release of dexamethasone. METHODS: The in vitro release of dexamethasone was investigated and the implant degradation was monitored by the percent of mass loss and by changes in the surface morphology. Differential scanning calorimetry was used to evaluate stability and interaction of the implant and the drug. The short-term tolerance of the implants was studied after intravitreous implantation in rabbit eye. Results: PCL implant allows for a controlled and prolonged delivery of dexamethasone since it releases 25% of the drug in 21 weeks. Its low degradation rate was confirmed by the mass loss and scanning electron microscopy studies. Preliminary observations show that PCL intravitreous implants are very well tolerated in the rabbit eye. CONCLUSION: This study demonstrates the PCL drug delivery systems allowed to a prolonged release of dexamethasone in vitro. The implants demonstrated a strikingly good intraocular short-term tolerance in rabbits eyes. The in vitro and preliminary in vivo studies tend to show that PCL implants could be of interest when long-term sustained intraocular delivery of corticosteroids is required

Poly-epsilon-caprolactone intravitreous devices: an in vivo study.

PURPOSE: The objective of this study was to evaluate the long-term safety and pharmacokinetic profile of a dexamethasone-loaded poly-epsilon-caprolactone (PCL) intravitreous implant. METHODS: The PCL devices were prepared by compression and were inserted into the vitreous of pigmented rabbits. At different time points, vitreous samples were retrieved, and dexamethasone concentration was analyzed by high-performance liquid chromatography. The biodegradation of the implants was evaluated by scanning electron microscopy, and the dexamethasone remaining was evaluated at the end of follow-up. Clinical and histologic examinations were performed to evaluate the implant's tolerance. RESULTS: The PCL implant allows for a controlled and prolonged delivery of dexamethasone in rabbits eyes since it released the drug within the therapeutic range for at least 55 weeks. At 55 weeks approximately 79% of the drug was still present in the implant. Biodegradation study showed that PCL implants degradation is very slow. Clinical and histologic observations showed that the devices were very well tolerated in the rabbit eye. CONCLUSIONS: This study demonstrates the feasibility and tolerance of intravitreous PCL drug delivery systems, which can offer a wide range of applications for intraocular drug delivery because of their controlled and prolonged release over months or even years

Study Of The Release Potential Of The Antibiotic Gentamicin From Microspheres Of Bcp

Orthopedics surgeries frequently are open surgeries, but the improvement of the specific instrumentation and the use of bioresorbable polymerics implants for regeneration of bone fractures are contributing to the development of noninvasive techniques such as an injectable bone substitute. These injectable materials are composites, formed by a particulate ceramic phase and a polymeric phase, and have the advantages of combining bioactivity and the ability to control degradation and some mechanical properties. In addition, microparticles present flexibility to fill several types of defects with closer packing and allow new bone growth and vascularization through the interconnected pores formed by the spaces between them. Another advantage of the particulate materials is that they have the potential to incorporate drugs such as antibiotics that can be applied in situ for treatment or prevention of bone infection, which is important because the poor circulation of blood in the osseous tissues makes necessary large amounts of these drugs to guarantee that an adequate dose reaches the affected site. This work evaluates the release potential of gentamicin from BCP spherical microparticles to be used in osseous injectable implants. The particles present a smooth geometry to prevent inflammatory reactions frequently caused by an irregular morphology, and their compositions offer a combination of biodegradability and stability. Microparticles with diameters between 150-425μm, were obtained by a method based on the immiscibility of liquids. To encapsulate the antibiotic, the spheres were immersed in a gentamicin solution, and after 24h they were separated and dried. The evaluation of the gentamicin release from the microspheres was carried out at 37°C in PBS, and the release medium was collected at predetermined time intervals for measurement of the amount released. This work demonstrates that these microspheres can find potential application in bone repair and regeneration. © (2012) Trans Tech Publications.493-494269274Guastaldi, A.C., Aparecida, A.H., Fosfato de calcio de interesse biologico: Importancia como biomateriais, propriedades e metodos de obtencao de recobrimentos (2010) Quimica Nova, 33 (6), pp. 1352-1358Andrade, A.L., Domingues, R.Z., Ceramicas bioativas: Estado da arte (2006) Quimica Nova, 29 (1), pp. 100-104Grimandi, G., Weiss, P., Millot, F., Daculsi, G., In vitro evaluation of a new injectable calcium phosphate material (1998) Journal of Biomedical Materials Research, 39 (4), pp. 660-666. , DOI 10.1002/(SICI)1097-4636(19980315)39:43.0.CO;2-9Silva, G.A., Ducheyne, P., Reis, R.L., Materials in particulate form for tissue engineering. 1 Basic concepts (2007) Journal of Tissue Engineering and Regenerative Medicine, 1, pp. 4-24Komlev, V.S., Barinov, S.M., Koplik, E.V., A method to fabricate porous spherical hydroxyapatite granules intended for time-controlled drug release (2002) Biomaterials, 23 (16), pp. 3449-3454. , DOI 10.1016/S0142-9612(02)00049-2, PII S0142961202000492Ribeiro, C.C., Barrias, C.C., Barbosa, M.A., Preparation and characterisation of calcium-phosphate porous microspheres with a uniform size for biomedical applications (2006) Journal of Materials Science: Materials in Medicine, 17 (5), pp. 455-463. , DOI 10.1007/s10856-006-8473-xSivakumar, M., Panduranga Rao, K., Preparation, characterization, and in vitro release of gentamicin from coralline hydroxyapatite-alginate composite microspheres (2003) Journal of Biomedical Materials Research - Part A, 65 (2), pp. 222-228Laurent, F., Bignon, A., Goldnadel, J., Chevalier, J., Fantozzi, G., Viguier, E., Roger, T., Hartmann, D., A new concept of gentamicin loaded HAP/TCP bone substitute for prophylactic action: In vitro release validation (2008) Journal of Materials Science: Materials in Medicine, 19 (2), pp. 947-951. , DOI 10.1007/s10856-007-0163-9Paul, W., Sharma, C.P., Development of porous spherical hydroxyapatite granules: Application towards protein delivery (1999) Journal of Materials Science: Materials in Medicine, 10 (7), pp. 383-388. , DOI 10.1023/A:100891841219

Implants as drug delivery devices for the treatment of eye diseases

The treatment of diseases affecting the posterior segment of the eye is limited by the difficulty in transporting effective doses of drugs to the vitreous, retina, and choroid. Topically applied drugs are poorly absorbed due to the low permeability of the external ocular tissues and tearing. The blood-retina barrier limits drug diffusion from the systemic blood to the posterior segment, thus high doses of drug are needed to maintain therapeutic levels. In addition, systemic side effects are common. Intraocular injections could be an alternative, but the fast flowing blood supply in this region, associated with rapid clearance rates, causes drug concentration to quickly fall below therapeutic levels. To obtain therapeutic levels over longer time periods, polymeric sustained-drug release systems implanted within the vitreous are being studied for the treatment of vitreoretinal disorders. These systems are prepared using different kinds of biodegradable or non-biodegradable polymers. This review aims to demonstrate the main characteristics of these drug delivery implants and their potential for clinical application.<br>O tratamento de doenças do segmento posterior do olho é limitado pela dificuldade no transporte de doses efetivas de fármacos para o vítreo, retina e coróide. Os fármacos aplicados topicamente são pouco absorvidos por causa da baixa permeabilidade dos tecidos oculares externos e ao lacrimejamento. Embora a administração sistêmica seja capaz de transportar fármacos para o segmento posterior do olho, as barreiras hemato-aquosa e hematorretiniana dificultam a absorção e, normalmente, são necessárias doses elevadas, as quais estão geralmente associadas a potenciais efeitos adversos. Injeções intravitreais são capazes de transportar fármacos para o segmento posterior do olho, mas é uma técnica invasiva, pouco tolerada pelos pacientes e apresenta riscos de infecções oculares e danos aos tecidos. Visando a obtenção de níveis terapêuticos adequados de fármacos no segmento posterior do bulbo do olho por longos períodos, sistemas de liberação poliméricos implantados diretamente no vítreo estão sendo investigados para o tratamento de várias doenças vítreo-retinianas. Esses implantes podem ser preparados a partir de diferentes polímeros biocompatíveis, biodegradáveis ou não-biodegradáveis. Nesta revisão, as principais características destes implantes transportadores de fármacos são descritas, expondo suas potencialidades de aplicação clínica

A predatory mite as potential biological control agent of Diaphorina citri

Diaphorina citri Kuwayama (Hemiptera: Liviidae) is a vector of the bacteria that cause Huanglongbing, the fatal disease threatening citriculture worldwide. One of the most important management methods is the control of D. citri with pesticides, but their intensive use causes development of resistance and pollution. An alternative method is therefore necessary to manage this vector-pathogen system. The generalist predatory mite Amblyseius herbicolus Chant (Acari: Phytoseiidae) can be found on citrus and orange jasmine plants, important hosts of D. citri in Brazil. Here we show that this phytoseiid can reproduce and develop on D. citri eggs. The predation rate was higher on D. citri eggs collected from plants in the field than on eggs from small plants from a laboratory rearing. Yet the predator preferred eggs from the laboratory. This may indicate that the higher predation rate of eggs from the field served to compensate for these eggs being of lower nutritional quality. This was confirmed with a series of experiments with limited numbers of eggs. We conclude that Amblyseius herbicolus is a potential biological control agent of D. citri, and its performance and control may be affected by the quality of the host plant

A predatory mite as potential biological control agent of Diaphorina citri

Diaphorina citri Kuwayama (Hemiptera: Liviidae) is a vector of the bacteria that cause Huanglongbing, the fatal disease threatening citriculture worldwide. One of the most important management methods is the control of D. citri with pesticides, but their intensive use causes development of resistance and pollution. An alternative method is therefore necessary to manage this vector-pathogen system. The generalist predatory mite Amblyseius herbicolus Chant (Acari: Phytoseiidae) can be found on citrus and orange jasmine plants, important hosts of D. citri in Brazil. Here we show that this phytoseiid can reproduce and develop on D. citri eggs. The predation rate was higher on D. citri eggs collected from plants in the field than on eggs from small plants from a laboratory rearing. Yet the predator preferred eggs from the laboratory. This may indicate that the higher predation rate of eggs from the field served to compensate for these eggs being of lower nutritional quality. This was confirmed with a series of experiments with limited numbers of eggs. We conclude that Amblyseius herbicolus is a potential biological control agent of D. citri, and its performance and control may be affected by the quality of the host plant