A novel FK506-loading mesoporous silica nanoparticle homing to lymph nodes for transplant rejection treatment.
Int J Pharm
; 656: 124074, 2024 May 10.
Article
em En
| MEDLINE
| ID: mdl-38565406
ABSTRACT
Tacrolimus (FK506) is an effective therapeutic for transplant rejection in clinical practice, primarily inhibiting rejection by suppressing the activation and proliferation of allogeneic T cells in the lymph nodes (LNs). However, conventional administration methods face challenges in directly delivering free FK506 to the LNs. In this study, we introduce a novel LN-targeted delivery system based on mesoporous silica nanoparticles (MSNs-FK506-MECA79). These particles were designed to selectively target high endothelial venules in LNs; this was achieved through surface modification with MECA79 antibodies. Their mean size and zeta potential were 201.18 ± 5.98 nm and - 16.12 ± 0.36 mV, respectively. Our findings showed that MSNs-FK506-MECA79 could accumulate in LNs and increase the local concentration of FK506 from 28.02 ± 7.71 ng/g to 123.81 ± 76.76 ng/g compared with the free FK506 treatment group. Subsequently, the therapeutic efficacy of MSNs-FK506-MECA79 was evaluated in a skin transplantation model. The treatment with MSNs-FK506-MECA79 could lead to a decrease in the infiltration of T cells in the grafts, a reduction in the grade of rejection, and a significant prolongation of survival. Consequently, this study presents a promising strategy for the active LN-targeted delivery of FK506 and improving the immunotherapeutic effects on transplant rejection.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tacrolimo
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Dióxido de Silício
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Nanopartículas
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Rejeição de Enxerto
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Imunossupressores
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Linfonodos
Limite:
Animals
Idioma:
En
Revista:
Int J Pharm
Ano de publicação:
2024
Tipo de documento:
Article