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Comparative Study
. 2017 Nov;24(1):30-39.
doi: 10.1080/10717544.2016.1228713.

Hyaluronic acid-modified didecyldimethylammonium bromide/ d-a-tocopheryl polyethylene glycol succinate mixed micelles for delivery of baohuoside I against non-small cell lung cancer: in vitro and in vivo evaluation

Hongmei Yan  1   2 , Jie Song  1   2 , Xiaobin Jia  1   2 , Zhenhai Zhang  2
Affiliations
Comparative Study

Hyaluronic acid-modified didecyldimethylammonium bromide/ d-a-tocopheryl polyethylene glycol succinate mixed micelles for delivery of baohuoside I against non-small cell lung cancer: in vitro and in vivo evaluation

Hongmei Yan et al. Drug Deliv. 2017 Nov.

Abstract

Baohuoside I is an effective but a poorly soluble antitumor drug. In this study, we prepared baohuoside I-loaded mixed micelles with didecyldimethylammonium bromide (DDAB) and d-a-tocopheryl polyethylene glycol succinate (TPGS) (DTBM) and active targeting mixed micelles (HDTBM) with hyaluronic acid (HA) as the targeting ligand on the surface of the mixed micelles. We performed a systematic comparative evaluation of the antiproliferative effect, cellular uptake, antitumor efficacy, and in vivo tumor targeting of these micelles using A549 cells. HDTBM showed improved cellular uptake and had a greater hypersensitizing effect on A549 cell lines than baohuoside I; half-maximal inhibitory concentration (IC50) was 8.86 versus 20.42 μg/mL, respectively. Results of the antitumor efficacy study and the imaging study for in vivo targeting showed that the mixed-micelle formulation had higher antitumor efficacy and achieved effective and targeted drug delivery. Therefore, our results indicate that HA/baohuoside I-M may be used as a potential antitumor formulation.

Keywords: Baohuoside I; antitumor; hyaluronic acid; mixed micelles; targeting.

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Conflict of interest statement

The author(s) declare(s) that they have no conflicts of interest to disclose. This work was supported by the National Natural Science Foundation of China (81274088, 81303275).

Figures

Figure 1.
Figure 1.
Characteristics of the baohuoside I-loaded micelles. Size distribution of baohuoside I-loaded micelles (A). Baohuoside I release profiles from the micelles in vitro (B).Transmission electron microscope (TEM) image of baohuoside I-loaded micelles in 50 nm scale (C). Quotient of vibrational band intensities (I338/I333) from excitation spectra of pyrene as a function of lg c of mixed micelle in distilled water (D). Data are presented as the mean ± SD (n =3).
Figure 2.
Figure 2.
Cellular uptake efficiency of the baohuoside I and baohuoside I-loaded micelles by A549 cells after 1, 2 and 4 h incubation (A). Fluorescence microscope of A549 cells after 2 h incubation with the free fluorescent coumarin-6 and the coumarin-6-loaded mixed micelles (B).
Figure 3.
Figure 3.
In vivo antitumor study of baohuoside I-loaded micelles in Balb/c nude mice implanted with A549 cells. Tumor volumes (A) and body weight (B) were monitored daily. Tumor weight (C) and organ index (D) were monitored at the end of the experiment. The results were presented as the mean ± SD (n = 6). *p <0.05, compared with control group. #p < 0.05, compared with Baohuoside I group & p < 0.05, compared with DTBM group. H&E staining of liver and kidney sections excised from A549 tumor-bearing mice following 14 d treatment with HDTBM (E). Mice treated with paclitaxel and PBS were used as controls.
Figure 4.
Figure 4.
Fluorescence images of the mice bearing A549 cells on right sides at different time points after intravenous injection (A) and the distribution of DiR in various important organs (B).
Figure 5.
Figure 5.
Graphical representation of internalization and accumulation of free drug and micelles modified by TPGS and HA in resistant A549 cells.
See this image and copyright information in PMC

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