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Linear–Dendritic Copolymer Composed of Polyethylene Glycol and All-trans-Retinoic Acid as Drug Delivery Platform for Paclitaxel against Breast Cancer
journal contribution
posted on 2015-03-18, 00:00 authored by Jianfeng Li, Xutao Jiang, Yubo Guo, Sai An, Yuyang Kuang, Haojun Ma, Xi He, Chen JiangA new
linear–dendritic copolymer composed of poly(ethylene
glycol) (PEG) and all-trans-retinoic acid (ATRA) was synthesized as
the anticancer drug delivery platform (PEG-G3-RA8). It
can self-assemble into core–shell micelles with a low critical
micelle concentration (CMC) at 3.48 mg/L. Paclitaxel (PTX) was encapsulated
into PEG-G3-RA8 to form PEG-G3-RA8/PTX micelles
for breast cancer treatment. The optimized formulation had high drug
loading efficacy (20% w/w of drug copolymer ratio), nanosized diameter
(27.6 nm), and narrow distribution (PDI = 0.103). Compared with Taxol,
PEG-G3-RA8/PTX remained highly stable in the serum-containing
cell medium and exhibited 4-fold higher cellular uptake. Besides,
near-infrared fluorescence (NIR) optical imaging results indicated
that fluorescent probe loaded micelle had a preferential accumulation
in breast tumors. Pharmacokinetics and biodistribution studies (10
mg/kg) showed the area under the plasma concentration–time
curve (AUC0‑∞) and mean residence time (MRT0‑∞) for PEG-G3-RA8/PTX and Taxol
were 12.006 ± 0.605 mg/L h, 2.264 ± 0.041 h and 15.966 ±
1.614 mg/L h, 1.726 ± 0.097 h, respectively. The tumor accumulation
of PEG-G3-RA8/PTX group was 1.89-fold higher than that
of Taxol group 24 h postinjection. With the advantages like efficient
cellular uptake and preferential tumor accumulation, PEG-G3-RA8/PTX showed superior therapeutic efficacy on MCF-7 tumor bearing
mice compared to Taxol.