Preclinical evaluation of methotrexate-loaded polyelectrolyte complexes and thermosensitive hydrogels as treatment for rheumatoid arthritis.

This work proposes new methotrexate (MTX) loaded drug delivery systems (DDS) to treat rheumatoid arthritis via the intra-articular route: a poloxamer based thermosensitive hydrogel (MTX-HG), oligochitosan and hypromellose phthalate-based polyelectrolyte complexes (MTX-PEC) and their association (MTX-PEC-HG). MTX-PEC showed 470 ± 166 nm particle size, 0.298 ± 0.108 polydispersity index, +26 ± 2 mV and 74.3 ± 5.8% MTX efficiency entrapment and particle formation was confirmed by infrared spectroscopy and thermal analysis. MTX-HG and MTX-PEC-HG gelled at 36.7°C. MTX drug release profile was prolonged for MTX-HG and MTX-PEC-HG, and faster for MTX-PEC and free MTX. The in vivo effect of the MTX-DDSs systems was evaluated in induced arthritis rats as single intra-articular dose. The assessed parameters were the mechanical nociceptive threshold, the plasmatic IL-1ß level and histological analysis of the tibiofemoral joint. MTX-HG and MTX-PEC-HG performance were similar to free MTX and worse than oral MTX, used as positive control. All DDSs showed some irritative effect, for which further studies are required. MTX-PEC was the best treatment on recovering cartilage damage and decreasing allodynia. Thus, MTX-PEC demonstrated potential to treat rheumatoid arthritis, with the possibility of decreasing the systemic exposure to the drug.

Investigation of the Involvement of the Endocannabinoid System in TENS-Induced Antinociception.

Transcutaneous electrical nerve stimulation (TENS) promotes antinociception by activating the descending pain modulation pathway and consequently releasing endogenous analgesic substances. In addition, recent studies have shown that the endocannabinoid system controls pain. Thus, the present study investigated the involvement of the endocannabinoid system in TENS-induced antinociception of cancer pain using a cancer pain model induced by intraplantar (i.pl.) injections of Ehrlich tumor cells in male Swiss mice. Low- and high-frequency TENS was applied for 20 minutes to the mice's paws, and to investigate the involvement of the endocannabinoid system were used the N-(peperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pitazole-3-carboixamide (AM251), a cannabinoid CB1 receptor antagonist and (5Z,8Z,11Z,14Z)-5,8,11,14-eicosatetraenyl-methylester phosphonofluoridic acid (MAFP), an inhibitor of the endocannabinoid metabolizing enzyme fatty acid amide hydrolase, injected by via i.pl., intrathecal (i.t.), and intradorsolateral periaqueductal gray matter (i.dl.PAG). Furthermore, liquid chromatography-tandem mass spectrometry, western blot, and immunofluorescence assays were used to evaluate the endocannabinoid anandamide levels, cannabinoid CB1 receptor protein levels, and cannabinoid CB1 receptor immunoreactivity, respectively. Low- and high-frequency TENS reduced the mechanical allodynia induced by Ehrlich tumor cells and this effect was reversed by AM251 and potentiated by MAFP at the peripheral and central levels. In addition, TENS increased the endocannabinoid anandamide levels and the cannabinoid CB1 receptor protein levels and immunoreactivity in the paw, spinal cord, and dorsolateral periaqueductal gray matter. These results suggest that low- and high-frequency TENS is effective in controlling cancer pain, and the endocannabinoid system is involved in this effect at both the peripheral and central levels. PERSPECTIVE: TENS is a nonpharmacological strategy that may be used to control cancer pain. Identification of a new mechanism involved in its analgesic effect could lead to the development of clinical studies as well as an increase in its application, lessening the need for pharmacological treatments.

Influência do tratamento do câncer na rotação pélvica avaliada por baropodometria / Influence of cancer treatment on pelvic rotation assessed by baropodometry

Introdução: O câncer tem sido um crescente problema de saúde pública no Brasil. Comumente, a pessoa com câncer pode apresentar diversas alterações posturais, como a rotação da pelve, ocasionadas pela doença e por efeitos adversos secundários às formas de tratamento. Objetivo: Analisar a influência do posicionamento rotacional da pelve de pessoas com câncer por meio da baropodometria. Métodos: Foram incluídos 45 indivíduos, divididos em: Grupo Quimioterapia e/ou Radioterapia (GQR), Grupo Câncer em Acompanhamento (GCA) e Grupo Controle sem Câncer (GCS). Todos os voluntários foram avaliados quanto ao posicionamento da pelve por meio da baropodometria. Resultados: Não foram encontradas alterações significativas no posicionamento rotacional da pelve nas comparações entre os grupos com câncer e grupo controle (p: 0,112; Poder: 0,838; f2: 1,121). Conclusão: Os resultados sugerem que o câncer e suas formas de tratamento não exerceram influência sobre a postura rotacional da pelve. (AU)

Introduction: Cancer has been a growing public health problem in Brazil. Patients with cancer may commonly present a number postural changes such as the pelvis rotation due to the disease itself and also to secondary adverse effects produced by its forms of treatment. Objective: To assess the rotational positioning of the pelvis in cancer patients using computerized baropodometry. Methods: A total of 45 volunteers were divided into: Chemotherapy combined with radiotherapy Group (QRG), Follow up Cancer Group (CAG) and Control Group without Cancer (CG). All subjects were assessed for the positioning of the pelvis using baropodometry Results: No significant changes were found in the rotational positioning of the pelvis in the comparison between the cancer groups and the control group (p: 0,112; Power: 0,838; Effect: 1,121). Conclusion: The results suggest that the cancer and its forms of treatment have no influence on the rotational posture of the pelvis. (AU)