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Int J Mol Sci ; 21(15)2020 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-32748844

RESUMO

Ongoing aortic wall degeneration and subsequent aneurysm exclusion failure are major concerns after an endovascular aneurysm repair with a stent-graft. An ideal solution would be a drug therapy that targets the aortic wall and inhibits wall degeneration. Here, we described a novel drug delivery system, which allowed repetitively charging a graft with therapeutic drugs and releasing them to the aortic wall in vivo. The system was composed of a targeted graft, which was labeled with a small target molecule, and the target-recognizing nanocarrier, which contained suitable drugs. We developed the targeted graft by decorating a biotinylated polyester graft with neutravidin. We created the target-recognizing nanocarrier by conjugating drug-containing liposomes with biotinylated bio-nanocapsules. We successfully demonstrated that the target-recognizing nanocarriers could bind to the targeted graft, both in vitro and in blood vessels of live mice. Moreover, the drug released from our drug delivery system reduced the expression of matrix metalloproteinase-9 in mouse aortas. Thus, this hybrid system represents a first step toward an adjuvant therapy that might improve the long-term outcome of endovascular aneurysm repair.


Assuntos
Aorta/efeitos dos fármacos , Aneurisma Aórtico/terapia , Prótese Vascular , Sistemas de Liberação de Medicamentos/métodos , Metaloproteinase 9 da Matriz/metabolismo , Quinolinas/administração & dosagem , Animais , Aorta/metabolismo , Aorta/patologia , Avidina/química , Portadores de Fármacos/química , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/química , Masculino , Camundongos Endogâmicos C57BL , Microscopia de Fluorescência , Nanoestruturas/química , Desenho de Prótese , Quinolinas/química , Resultado do Tratamento
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