Reduction-sensitive mixed micelles for selective intracellular drug delivery to tumor cells and reversal of multidrug resistance.
Int J Pharm
; 550(1-2): 1-13, 2018 Oct 25.
Article
em En
| MEDLINE
| ID: mdl-30114451
ABSTRACT
Stimuli-responsive nanocarriers have demonstrated their potentials in optimizing chemotherapeutics and anticancer efficacy. In this study, a mixed micelle system (THSP) was prepared by combining reduction-sensitive hyaluronic acid-poly(lactide) (HA-ss-PLA) conjugates and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), with objective to achieve multiple functionalities of selective intracellular rapid release, active targeting capability and multidrug resistance reversal. The mixed micelle possessed desirable particle diameter of 124.32â¯nm and high entrapment efficiency at 87.97%. Importantly, the THSP mixed micelles demonstrated good stability in systemic circulation and rapidly released PTX in intracellular reductive environment. In vitro cellular uptake study and cytotoxicity assay indicated that the mixed micelles effectively increased drug accumulation in A549 cells and Taxol resistant A549/Taxol cells, and inhibited growth of tumor cells. In addition, the redox-responsive THSP micelles preferentially accumulated to the tumor site and improved anticancer drug activity in vivo, with a TIR of 69.08%. It was concluded that redox-sensitive mixed micelles THSP provided a potential vehicle for efficient anticancer drug delivery and enhancement in treating MDR tumor in the future.
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Base de dados:
MEDLINE
Assunto principal:
Sistemas de Liberação de Medicamentos
/
Micelas
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article