期刊
ADVANCED HEALTHCARE MATERIALS
卷 3, 期 9, 页码 1508-1517出版社
WILEY
DOI: 10.1002/adhm.201300638
关键词
drug delivery; micelles; polypeptides; DPD simulation
资金
- National Natural Science Foundation of China [21234002, 51303055]
- Ministry of Education [313020]
- National Basic Research Program of China [2012CB933600]
- Research Fund for the Doctoral Program of Higher Education of China [20120074120001]
- Shanghai municipality [10GG15, 12ZR1442500]
- Fundamental Research Funds for the Central Universities [WD1214008]
A dual-drug-loaded micelle is designed and constructed from a mixture of poly(propylene oxide)-b-poly(-benzyl-l-glutamate)-b-poly(ethylene glycol) (PPO-b-PBLG-b-PEG) triblock terpolymers and two model drugs, doxorubicin (DOX) and naproxen (Nap). In the micelles, the DOX is chemically linked to the PBLG backbones through an acid-cleavable hydrazone bond, whereas the Nap is physically encapsulated in the cores. The drug loading and releasing behaviors of the dual-drug-loaded micelles as well as single drug-loaded micelles (DOX-conjugated or Nap-loaded micelles) are studied. The structures of micelles are characterized by means of microscopies and dynamic light scattering, and further examined by dissipative particle dynamics (DPD) simulations. It is revealed that the micelles possess a core-shell-corona structure in which the PPO/Nap, PBLG/DOX, and PEG aggregate to form the core, shell, and corona, respectively. In vitro studies reveal that the release of DOX and Nap is pH- and thermosensitive. Such drug releasing behaviors are also examined by DPD simulations, and more information regarding the mechanism is obtained. In addition, the bio-related properties such as cellular uptake of the micelles and biocompatibility of the deliveries are evaluated. The results show that the dual-drug-loaded micelles are biocompatible at normal physiological conditions and retain the anti-cancer efficiency.
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