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1.
Xenotransplantation ; 20(4): 219-26, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23789985

RESUMO

Islet cell transplantation is a promising option for the restoration of normal glucose homeostasis in patients with type 1 diabetes. Because graft volume is a crucial issue in islet transplantations for patients with diabetes, we evaluated a new method for increasing functional tissue yield in xenogeneic grafts of encapsulated islets. Islets were labeled with three different superparamagnetic iron oxide nano particles (SPIONs; dextran-coated SPION, siloxane-coated SPION, and heparin-coated SPION). Magnetic separation was performed to separate encapsulated islets from the empty capsules, and cell viability and function were tested. Islets labeled with 1000 µg Fe/ml dextran-coated SPIONs experienced a 69.9% reduction in graft volume, with a 33.2% loss of islet-containing capsules. Islets labeled with 100 µg Fe/ml heparin-coated SPIONs showed a 46.4% reduction in graft volume, with a 4.5% loss of capsules containing islets. No purification could be achieved using siloxane-coated SPIONs due to its toxicity to the primary islets. SPION labeling of islets is useful for transplant purification during islet separation as well as in vivo imaging after transplantation. Furthermore, purification of encapsulated islets can also reduce the volume of the encapsulated islets without impairing their function by removing empty capsules.


Assuntos
Separação Celular/métodos , Compostos Férricos , Transplante das Ilhotas Pancreáticas/métodos , Ilhotas Pancreáticas/citologia , Magnetismo , Nanopartículas , Transplante Heterólogo/métodos , Animais , Contagem de Células , Sobrevivência Celular/fisiologia , Dextranos , Heparina , Humanos , Ilhotas Pancreáticas/fisiologia , Imageamento por Ressonância Magnética , Ratos , Ratos Wistar , Siloxanas
2.
Biomaterials ; 218: 119331, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31299455

RESUMO

Various types of particle-based drug delivery systems have been explored for the treatment of pulmonary diseases; however, bio-distribution and elimination of the particles should be monitored for better understanding of their therapeutic efficacy and safety. This study aimed to characterize the biological properties of micro-sized discoidal polymeric particles (DPPs) as lung-targeted drug delivery carriers. DPPs were prepared using a top-down fabrication approach and characterized by assessing size and zeta potential. They were labeled with zirconium-89 (89Zr), and bio-distribution studies and PET imaging were performed for 7 days after intravenous administration. Their hydrodynamic size was 2.8 ±â€¯6.1 µm and average zeta potential was -39.9 ±â€¯5.39 mV. At doses of 5, 12.5, and 25 mg/kg, they showed no acute toxicity in nude mice. Desferrioxamine (DFO)-functionalized 89Zr-labeled DPPs gave a decay-corrected radiochemical yield of 82.1 ±â€¯0.2%. Furthermore, 89Zr-DPPs, from chelate-free labeling methods, showed a yield of 48.5 ±â€¯0.9%. Bio-distribution studies and PET imaging showed 89Zr-DFO-DPPs to be mainly accumulated in the lungs and degraded within 3 d of injection. However, 89Zr-DFO-DPPs showed significantly low uptake in the bone. Overall, our results suggested micro-sized DPPs as promising drug delivery carriers for the targeted treatment of various pulmonary diseases.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Polímeros/química , Animais , Desferroxamina/química , Feminino , Imunofluorescência , Humanos , Pneumopatias/tratamento farmacológico , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Tomografia por Emissão de Pósitrons/métodos , Radioisótopos/química , Temperatura , Zircônio/química
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