RESUMO
BACKGROUND: Leishmaniasis is a neglected disease endemic in tropical and subtropical areas, with an incidence about 1.6 million cases/year. The first-line treatment of this disease is pentavalent antimony, and the second-line are pentamidine and amphotericin B. All the treatments available cause severe side effects and often have difficulty in accessing parasites within infected cells. STUDY QUESTION: This study aimed to determine if the use of nanoparticles loaded with meglumine antimoniate could reach and targeting infected organs with leishmaniasis, reducing the dosage used and promoting less adverse effects. STUDY DESIGN: This study was performed comparing the meglumine nanoparticle in two experimental groups. The first one healthy mice and the second one inducted mice (leishmaniasis). MEASURES AND OUTCOMES: The nanoparticles loaded with meglumine antimoniate (nanoantimony) were prepared by double-emulsion solvent evaporation method and showed a size of about 150-200 nm. BALB/c mice infected or not with Leishmania amazonensis (cutaneous leishmaniasis model) or Leishmania infantum (visceral leishmaniasis model) was used to access the biodistribution of nanoantimony and meglumine antimoniate labeled with technetium-99m. RESULTS: The biodistribution profiles showed a preferential targeting of the nanoparticles to the liver, spleen, and lungs. Because these are the main organs infected, the nanoparticle may be used for this purpose. The results for cutaneous leishmaniasis showed a low uptake by the lesion (infected region). CONCLUSIONS: The results demonstrated the potential use of these nanoparticles to improve the efficacy of meglumine antimoniate in the treatment of visceral leishmaniasis, indicating their potential as an alternative therapeutic strategy for leishmaniasis infections.
Assuntos
Antiprotozoários/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Visceral/tratamento farmacológico , Antimoniato de Meglumina/administração & dosagem , Animais , Modelos Animais de Doenças , Humanos , Leishmania infantum/patogenicidade , Leishmania mexicana/patogenicidade , Leishmaniose Cutânea/parasitologia , Leishmaniose Visceral/parasitologia , Antimoniato de Meglumina/farmacocinética , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Poliésteres/química , Tecnécio/química , Distribuição Tecidual , Resultado do TratamentoRESUMO
Monoclonal antibodies as polymeric nanoparticles are quite interesting and endow this new drug category with many advantages, especially by reducing the number of adverse reactions and, in the case of radiopharmaceuticals, also reducing the amount of radiation (dose) administered to the patient. In this study, a nanoradiopharmaceutical was developed using polylactic acid (PLA)/polyvinyl alcohol (PVA)/montmorillonite (MMT)/trastuzumab nanoparticles labeled with technetium-99m (99mTc) for breast cancer imaging. In order to confirm the nanoparticle formation, atomic force microscopy and dynamic light scattering were performed. Cytotoxicity of the nanoparticle and biodistribution with 99mTc in healthy and inducted animals were also measured. The results from atomic force microscopy showed that the nanoparticles were spherical, with a size range of ~200-500 nm. The dynamic light scattering analysis demonstrated that over 90% of the nanoparticles produced had a size of 287 nm with a zeta potential of -14,6 mV. The cytotoxicity results demonstrated that the nanoparticles were capable of reaching breast cancer cells. The biodistribution data demonstrated that the PLA/PVA/MMT/trastuzumab nanoparticles labeled with 99mTc have great renal clearance and also a high uptake by the lesion, as ~45% of the PLA/PVA/MMT/trastuzumab nanoparticles injected were taken up by the lesion. The data support PLA/PVA/MMT/trastuzumab labeled with 99mTc nanoparticles as nanoradiopharmaceuticals for breast cancer imaging.
RESUMO
The use of nanoparticles is under intense investigation. The possible advantages proposed by these systems are very impressive and the results may be quite schemer. In this scenario, the association of nanoparticles with radioactive materials (radionuclide) may be the most important step since the discovery of radioactive for nuclear medicine and radiopharmacy, especially for cancer targeting and therapy. In this study, we developed radiolabelled nanoparticles of hydroxyapatite with technetium 99m for bone cancer imaging. The results demonstrated that it is possible to label nanoparticles of hydroxyapatite, and due to its physicochemical properties is possible to develop nano-radiopharmaceutical for bone imaging.
Assuntos
Sangue/metabolismo , Rim/metabolismo , Tecnécio/farmacocinética , Animais , Materiais Biocompatíveis/química , Química Farmacêutica/tendências , Descoberta de Drogas , Durapatita/química , Humanos , Camundongos , Terapia de Alvo Molecular , Nanopartículas/química , Tecnécio/química , Distribuição TecidualRESUMO
Nanotechnology is attracting increasing attention worldwide. This study was made use of modern technology to decipher most of the intriguing biological aspects of nanoparticles. Labeling with technetium-99m ((99m)Tc) of six nanoparticles using different compositions and formulations, as well as complete biodistribution studies in mice was done. The results showed that the behaviors of nanoparticles were very different from each other. Mesoporous silica showed a high affinity for lung tissue, whereas polymeric nanoparticles were rapidly recognized and metabolized by the liver. The six nanoparticles showed different renal clearance times, suggesting that their area mechanisms of action were related to interaction and solubility. The labeling process in all samples showed similar results (all >99%). Biodistribution was demonstrated to be important for the study of nanoparticles, and could be used to predict the possible mechanism of action of nanoparticles.