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Despite the good clinical efficacy of interferon-alpha (IFNα) to treat some types of cancer and viral infections, this biological drug is underused given its severe adverse effects and high dosing parenteral regimens. Aiming to achieve a breakthrough in therapy with IFNα, this work reports for the first time on the design and full characterization of a novel nanomedicine of IFNα-2b-loaded chitosan nanoparticles (IFN-CT NPs) for oral delivery. IFN-CT NPs produced by ionotropic gelation, encapsulating approximately 100% of the drug, showed a size of 36 ± 8 nm, zeta potential of +30 mV (dynamic light scattering), and spherical morphology (transmission electron microscopy). The antiviral activity of IFN-CT NPs in vitro was comparable to that of commercial IFNα. Remarkably, both treatments stimulated the expression of IFN response genes to a similar extent in both noninfected and infected cells with Human Lymphotropic-T Virus type 1. Finally, oral administration of IFN-CT NPs (0.3 MIU) to CF1 mice showed detectable levels of IFNα in plasma after 1 h, whereas no IFNα was detected with a commercial formulation. These results are encouraging and open a new avenue for the administration of this biological drug in a minimally invasive, safer, and more patient-compliant way.

SUMMARY:Today, alternatives methods are developed for the use of laboratory animals for teaching, research and surgical training. In our work we present a novel alternative to the use of rats, by developing a technique of plastination at room temperature. High-quality rat preparations from the anatomical dissection point of view were obtained, in order to indefinitely preserve them dry, the thoracic and abdominal organs conserve its natural volume and shape, maintaining their texture and color. No odors or hassles and toxic vapors of conventional preserving agents were found. This technique allows the collection of dry, completely biosafe and durable specimens in a short time and with excellent quality. Plastination in laboratory rats complements undergraduate and postgraduate anatomy studies perfectly. Also, radiology and surgery may benefit from this technique.

Female Wistar rats are frequently used in experimental models to study hormone and bone pathologies and treatments. Most experimental studies involving histomorphometric evaluation assessed long bones, and few reports also studied mandibular bone. The aim of this work was to clarify and distinguish the age-related histomorphometric changes that occur in the tibia (subchondral bone) and in the mandible (interradicular bone), and thus obtain reference histomorphometric data of healthy female Wistar rats at different growth stages. Three groups of 8 healthy female Wistar rats were euthanized at 6 (GI), 10 (GII), and 14 (GIII) weeks. The tibiae and mandible were resected and histologically processed to obtain H&E stained sections of the tibia and the lower first molar to analyze the following histomorphometric parameters: Bone volume, trabecular width, trabecular number (Th.N)(1/mm), growth cartilage width, hypertrophic cartilage width and number of osteoclasts per area in the tibiae, and bone volume and number of osteoclasts per area N.Oc/mm2 in the interradicular bone of the first lower molar. A significant decrease in subchondral bone volume as a result of a decrease in trabecular number and growth cartilage width was observed in 14-week-old rats. Conversely, interradicular bone volume was found to increase with age. The results highlight the importance of analyzing both types of bone to better understand the response of two different trabecular bones, contributing in turn to decision making regarding treatment strategies and disease management.

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Interferon alpha (IFNα) is a protein drug used to treat viral infections and cancer diseases. Due to its poor stability in the gastrointestinal tract, only parenteral administration ensures bioavailability, which is associated with severe side effects. We hypothesized that the nanoencapsulation of IFNα within nanoparticles of the mucoadhesive polysaccharide chitosan would improve the oral bioavailability of this drug. In this work, we produced IFNα-loaded chitosan nanoparticles by the ionotropic gelation method. Their hydrodynamic diameter, polydispersity index and concentration were characterized by dynamic light scattering and nanoparticle tracking analysis. After confirming their good cell compatibility in Caco-2 and WISH cells, the permeability of unmodified and poly(ethylene glycol) (PEG)-modified (PEGylated) nanoparticles was measured in monoculture (Caco-2) and co-culture (Caco-2/HT29-MTX) cell monolayers. Results indicated that the nanoparticles cross the intestinal epithelium mainly by the paracellular route. Finally, the study of the oral pharmacokinetics of nanoencapsulated IFNα in BalbC mice revealed two maxima and area-under-the-curve of 56.9 pg*h/mL.

Distraction osteogenesis (DO) is a surgical technique producing bone lengthening by distraction of the fracture callus. Although a large number of experimental studies on the events associated with DO of craniofacial skeleton have been reported, the few employing rat mandibular bone DO used complicated designs and produced a small volume of newly formed bone. Thus, this study aims to present an original experimental model of mandibular DO in edentulous rats that produces a sufficient quantity and quality of intramembranous bone. Eight male Wistar rats, weighing 75 g, underwent extraction of lower molars. With rats weighing 350 g, right mandibular osteotomy was performed and the distraction device was placed. The distraction device was custom made using micro-implants, expansion screws, and acrylic resin. Study protocol: latency: 6 days, distraction: ¼ turn (0.175 mm) once a day during 6 d, consolidation: 28 d after distraction phase, sacrifice. DO-treated and contralateral hemimandibles were dissected and compared macroscopically and using radiographic studies. Histological sections were obtained and stained with H&E. A distraction gap filled with newly formed and mature bone tissue was obtained. This model of mandibular DO proved useful to obtain adequate quantity and quality of bone to study bone regeneration

Little is known about the early response of bone metabolism to hyperglycemia, or transient hyperglycemia, caused by poor compliance with treatment or inadequate control of diabetes in patients with type 1 diabetes. There are no studies comparing early diabetes-related alterations in endochondral ossification with those occurring through time. In order to histomorphometrically evaluate the growth cartilage and subchondral bone of male Wistar rat tibia shortly after experimentally inducing type 1 diabetes, thirty-five male Wistar rats were divided into 5 groups: Group A: control; Group B: induction of diabetes; euthanasia at one week; Group C: induction of diabetes plus insulin treatment; euthanasia at one week; Group D: induction of diabetes; euthanasia at six weeks; Group E: induction of diabetes plus insulin treatment; euthanasia at six weeks. Diabetes was induced by single intraperitoneal injection of 60mg/kg body weight of streptozotocin dissolved in citrate buffer pH 4.0. Two days after inducing diabetes, treatment with subcutaneously injected human insulin was initiated, according to protocol. The following parameters were evaluated: Tibial subchondral bone volume; trabecular area; bone surface; trabecular number; trabecular thickness. Tibial subchondral bone volume and epiphyseal cartilage width were significantly lower in both experimental groups as compared to controls. Insulin treatment resulted in values similar to controls. As shown by the microarchitecture of subchondral trabecular bone, all parameters were lower in diabetic animals, except for trabecular width which was similar to that observed in controls. The alteration in bone metabolism manifests in long bones very early in the course of diabetes, suggesting it would be advisable to analyze bone response as soon as possible following diagnosis of the disease, in order to prescribe treatments aimed at preventing further alterations in bone architecture.