pubs.acs.org/Langmuir
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2010 American Chemical Society
Self-Assembled Micelles from an Amphiphilic Hyperbranched Copolymer
with Polyphosphate Arms for Drug Delivery
Jinyao Liu, Wei Huang,* Yan Pang, Xinyuan Zhu, Yongfeng Zhou, and Deyue Yan*
School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites,
Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China
Received February 16, 2010. Revised Manuscript Received March 31, 2010
A novel type of amphiphilic hyperbranched multiarm copolymer [H40-star-(PLA-b-PEP-OH)] was synthesized
through a two-step ring-opening polymerization (ROP) procedure and applied to drug delivery. First, Boltorn H40 was
used as macroinitiator for the ROP of
L-lactide to form the intermediate (H40-star-PLA-OH). Then, the ROP of ethyl
ethylene phosphate was further initiated to produce H40-star-(PLA-b-PEP-OH). The resulting hyperbranched multi-
1
13
31
arm copolymers were characterized by H, C, and P NMR, GPC, and FTIR spectra. Benefiting from the amphiphilic
structure, H40-star-(PLA-b-PEP-OH) was able to self-assemble into micelles in water with an average diameter of
1
30 nm. In vitro evaluation of these micelles demonstrated their excellent biocompatibility and efficient cellular uptake
by methyl tetrazolium assay, flow cytometry, and confocal laser scanning microscopy measurements. Doxorubicin-
loaded micelles were investigated for the proliferation inhibition of a Hela human cervical carcinoma cell line, and the
Doxorubicin dose required for 50% cellular growth inhibition was found to be 1 μg/mL. These results indicate that
H40-star-(PLA-b-PEP-OH) micelles can be used as safe, promising drug-delivery systems.
15-20
Introduction
in recent years.
The unimolecular micelle does not disassemble
in the dilute solution and is stable to environmental changes
in vivo. Besides the good stability, the highly branched structure of
hyperbranched multiarm copolymers can provide many nanocav-
ities for drug encapsulation. Consequently, many double hydro-
philic or amphiphilic hyperbranched multiarm copolymers have
During the past two decades, various polymeric micelles have
been developed for potential application as a delivery vehicle
1-3
for small-molecule drugs.
Amphiphilic copolymers can self-
assemble into micelles in aqueous solution through the hydro-
phobic interactions among thecore-formingsegments. The hydro-
phobic inner core serves as a container for hydrophobic drugs, and
the outer shell composed of hydrophilic polymers maintains a
21-37
been prepared.
Most of them have poly(ethylene glycol)
4-10
hydration barrier to provide colloidal stability.
These micelles
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*Corresponding authors. E-mail: hw66@sjtu.edu.cn, dyyan@sjtu.edu.cn.
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Langmuir 2010, 26(13), 10585–10592
Published on Web 04/12/2010
DOI: 10.1021/la1006988 10585