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Polypeptide‐Based “Smart” Micelles for Dual‐Drug Delivery: A Combination Study of Experiments and Simulations
Author(s) -
Chen Lili,
Jiang Tao,
Cai Chunhua,
Wang Liquan,
Lin Jiaping,
Cao Xuguang
Publication year - 2014
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201300638
Subject(s) - micelle , dissipative particle dynamics , materials science , drug delivery , ethylene glycol , nanocarriers , dynamic light scattering , chemical engineering , chemistry , organic chemistry , biophysics , nanoparticle , nanotechnology , polymer , aqueous solution , engineering , biology
A dual‐drug‐loaded micelle is designed and constructed from a mixture of poly(propylene oxide)‐ b ‐poly(γ‐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.