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Macromol Biosci ; 19(4): e1800478, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30694599

RESUMO

The use of natural compounds to construct biomaterials, including delivery system, is an attractive strategy. In the present study, through threading functional α-cyclodextrins onto the conjugated macromolecules of poly(ethylene glycol) (PEG) and natural compound bile acid, glycopolymers of polyrotaxanes with the active targeting ability are obtained. These glycopolymers self-assemble into micelles as evidenced by dynamic light scattering and transmission electron microscopy, in which glucosamine, as an example of targeting groups, is introduced. These micelles after loading doxorubicin (DOX) exhibit the selective recognition with cancer cells 4T1. Meanwhile, the maximal half inhibitory concentration is determined to be ≈2.5 mg L-1 for the DOX-loaded micelles, close to the value of free DOX·HCl (1.9 mg L-1 ). The cumulative release of DOX at pH 5.5 is faster than at pH 7.4, which may be used as the controlled release system. This drug delivery system assembled by glycopolymers features high drug loading of DOX, superior biocompatibility. The strategy not only utilizes the micellization induced by bile acids, but also overcomes the major limitation of PEG such as the lack of targeting groups. In particular, this drug delivery platform can extend to grafting the other targeting groups, rendering this system more versatile.


Assuntos
Ácidos e Sais Biliares , Doxorrubicina , Portadores de Fármacos , Micelas , Neoplasias Experimentais/tratamento farmacológico , Rotaxanos , Animais , Ácidos e Sais Biliares/química , Ácidos e Sais Biliares/farmacocinética , Ácidos e Sais Biliares/farmacologia , Linhagem Celular Tumoral , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Camundongos , Células NIH 3T3 , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Coelhos , Rotaxanos/química , Rotaxanos/farmacocinética , Rotaxanos/farmacologia
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