RESUMO
The goal of the current study was to investigate the pharmacokinetic profile, tissue distribution and adverse effects of long-circulating liposomes (LCL) with curcumin (CURC) and doxorubicin (DOX), in order to provide further evidence for previously demonstrated enhanced antitumor efficacy in colon cancer models. The pharmacokinetic studies were carried out in healthy rats, following the i.v. injection of a single dose of LCL-CURC-DOX (1 mg/kg DOX). For the tissue distribution study, DOX concentration in tumours, heart and liver were measured after the administration of two i.v. doses of LCL-CURC-DOX (2.5 mg/kg DOX and 5 mg/kg CURC) to Balb/c mice bearing C26 colon tumours. Markers of murine cardiac and hepatic oxidative status were determined to provide additional insights into the benefit of co-encapsulating CURC and DOX in LCL over DOX-induced adverse effects in these organs. The current study demonstrated that the liposomal association of CURC and DOX effectively improved the pharmacokinetics and biodistribution of DOX, limiting its side effects, via CURC-dependent antioxidant effects.
Assuntos
Antibióticos Antineoplásicos/efeitos adversos , Antibióticos Antineoplásicos/farmacocinética , Carcinoma/tratamento farmacológico , Neoplasias do Colo/tratamento farmacológico , Curcumina/química , Doxorrubicina/efeitos adversos , Doxorrubicina/farmacocinética , Animais , Antibióticos Antineoplásicos/química , Cápsulas , Doxorrubicina/química , Lipossomos/química , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/tratamento farmacológico , Tamanho da Partícula , RatosRESUMO
BACKGROUND: Curcumin has antioxidative properties that could be useful in various diseases due to its ability to act on multiple targets of various cellular pathways. We aimed to assess the efficacy of liposomal curcumin compared with curcumin solution, when in addition to sumatriptan (ST) treatment, in an experimental migraine model induced with nitroglycerin (NTG) in rats. METHODS: Seven groups of 9 rats each were investigated: control group without migraine (1 mL saline solution intraperitoneal injection [ip]), control group with induced migraine, NTG+ST group (ST), NTG+ST+curcumin1 (CC1) group - 1 mg/100 g body weight (bw), NTG+ST+CC2 - 2 mg/100 g bw, NTG+ST+liposomal curcumin1 (lCC1) group - 1 mg/100 g bw, and NTG+ST+lCC2 (lCC2) group - 2 mg/100 g bw. NTG and ST were administered as 1 mL ip NTG | 1 mg/100 g bw and 1 mL ip ST | 1 mg/100 g bw, respectively. Plasma total oxidative stress (TOS), malondialdehyde (MDA), nitric oxide (NOx), thiol levels, as well as total antioxidative capacity (TAC) were assessed. The nociception process was assessed by counting the number of flinches and shakes after the formalin test. RESULTS: The plasma TOS, MDA, and NOx levels, as oxidative stress parameters, were significantly decreased in the curcumin-treated groups, especially where curcumin was in liposomal form. The thiol and TAC were also improved by the curcumin treatment, with the best results obtained for the liposomal curcumin. The closest number of flinches and shakes to the control group was obtained for the group treated with liposomal curcumin at a dose of 2 mg/100 g bw. CONCLUSION: Liposomal curcumin in a dose of 2 mg/100 g bw when in addition to ST treatment could be an optimum therapeutic strategy for migraine attacks and could represent a base for future clinical research and application.
Assuntos
Curcumina/administração & dosagem , Lipossomos/administração & dosagem , Transtornos de Enxaqueca/tratamento farmacológico , Sumatriptana/farmacologia , Administração Intravenosa , Animais , Modelos Animais de Doenças , Lipossomos/química , Masculino , Malondialdeído/sangue , Malondialdeído/metabolismo , Transtornos de Enxaqueca/induzido quimicamente , Óxido Nítrico/sangue , Óxido Nítrico/metabolismo , Nitroglicerina/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Medição da Dor , RatosRESUMO
Wound healing is a complex and dynamic process that involves modifying the wound environment depending on the patient's health status. Scar formation depends on many factors that influence wound healing, are important to bear in mind because most of the negative factors involved can be stopped by implementing an adequate treatment. The consensus in wound therapy recommends dressings that should keep a moist and alkaline environment thus creating a protective barrier against mechanical stress and secondary infections, in view of promoting granulation. In the current paper, we aimed to synthesize a polymer-based sponge containing chitosan-sodium hyaluronate-resveratrol (CHR) and to evaluate its regenerative potential. The process of synthesizing the CHR polymer was described before microtomography analysis was conducted and the density and porosity of the obtained sponges was assessed. The cytotoxicity was evaluated in vitro. By undertaking the in vivo testing of the CHR polymer, we aimed to determine the CHR sponge's potential to stimulate tissue regeneration after inflicting a controlled, reproducible and measurable skin wound in an animal model. Skin punch biopsies were harvested from the healed area and were subjected to histopathological evaluation. The results obtained in this study confirmed that this polymer accelerates the formation of granulation facilitating wound healing, while also achieving a bacteriostatic outcome.