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1.
Macromol Biosci ; 21(4): e2000392, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33506646

RESUMO

The excellent biocompatibility drug delivery system for effective treatment of glioma is still greatly challenged by the existence of blood-brain barrier, blood-brain tumor barrier, and the tissue toxicity caused by chemotherapy drugs. In this study, poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) is used for the first time for modifying third-generation poly(amidoamine) (PAMAM) to enhance their brain tumor-targeted drug delivery ability as well as simultaneously reducing the toxicity of PAMAM dendrimers and the tissue toxicity of the loaded doxorubicin (DOX). The cytotoxicity, the therapeutic ability in vitro, and the brain tumor-targeted ability of the PMPC modified PAMAM nanoparticles are further studied. Results indicate that PMPC, as a dual-functional modifier, can significantly reduce the cytotoxicity of PAMAM dendrimers, while efficiently target the brain tumor. In addition, the therapeutic effect of DOX-loaded PAMAM-PMPC in mice inoculated with U-87 is also studied in vivo. In comparison with DOX solution, DOX-loaded PAMAM-PMPC alleviates weight loss of tumor-inoculated mice and reduces the cardiotoxicity of DOX. The tumor growth inhibition, in vivo, is significantly increased up to (80.76 ± 1.66)%. In conclusion, this strategy of PMPC dual-functional targeted nanocarrier provides a new method for the delivery of chemotherapeutic drugs to treat glioma.


Assuntos
Dendrímeros/química , Doxorrubicina/administração & dosagem , Fosforilcolina/análogos & derivados , Ácidos Polimetacrílicos/química , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Neoplasias Encefálicas/tratamento farmacológico , Linhagem Celular Tumoral , Dendrímeros/farmacologia , Doxorrubicina/química , Portadores de Fármacos/uso terapêutico , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Glioma/tratamento farmacológico , Humanos , Luz , Espectroscopia de Ressonância Magnética , Camundongos , Nanopartículas , Fosforilcolina/química , Espalhamento de Radiação , Fatores de Tempo
2.
Int J Biol Macromol ; 153: 1251-1261, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31778704

RESUMO

Strong glue of mussels has long been considered as an ideal model to design synthetic bio-adhesives but the adhesive strength of metal-crosslinked mussel-inspired glues is not often satisfactory. Herein, inspired by the adhesive environment of mussels, we obtained metal-crosslinked ε-poly-L-lysine adhesives with high adhesive performance by introducing the elements of suitable adhesive environment (SAE) into the adhesives. The elements of SAE were clarified as weak alkaline conditions (pH ∼ 7.4) and low Fe3+ contents. The adhesive strength (∼105 kPa) of the metal-crosslinked adhesives endowed with the elements of SAE (PL-Cat/Fe-SAE) was about 8 times higher than that of fibrin glues. The high adhesive strength was found to originate from distinctive interfacial adhesion and cohesion strength of PL-Cat/Fe-SAE. PL-Cat/Fe-SAE showed strong interfacial adhesion capacity and nearly comparable cohesion strength to those PL-Cat/Fe adhesives with higher Fe3+ contents. The nearly comparable cohesion strength of PL-Cat/Fe-SAE was then found to be due to more amount of stable tris-complex existed in PL-Cat/Fe-SAE. In addition, PL-Cat/Fe-SAE was able to efficiently close the full thickness skin incisions. The study highlighted the importance of introducing SAE elements into the design of tissue adhesives and provided a facile and efficient strategy for constructing tissue adhesives with high adhesive performance.


Assuntos
Bivalves , Ferro/química , Polilisina/química , Adesivos Teciduais/química , Adesividade , Animais , Biomimética , Camundongos , Células NIH 3T3 , Reologia
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