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; Jie Song; Xiaobin Jia; Zhenhai Zhang

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

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

Authors

Hongmei Yan^{1

2}, Jie Song^{1

2}, Xiaobin Jia^{1

2}, Zhenhai Zhang²

Affiliations

¹ a College of Pharmacy, Nanjing University of Chinese Medicine , Nanjing , PR China and.
² b Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Third School of Clinical Medical of Nanjing University of Chinese Medicine , Nanjing , PR China.

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.

Publication types

Comparative Study

MeSH terms

Animals
Antineoplastic Agents, Phytogenic / administration & dosage*
Antineoplastic Agents, Phytogenic / chemistry
Antineoplastic Agents, Phytogenic / metabolism
Carcinoma, Non-Small-Cell Lung / drug therapy*
Carcinoma, Non-Small-Cell Lung / metabolism
Carcinoma, Non-Small-Cell Lung / pathology
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects
Dose-Response Relationship, Drug
Drug Carriers*
Drug Compounding
Flavonoids / administration & dosage*
Flavonoids / chemistry
Flavonoids / metabolism
Humans
Hyaluronic Acid / chemistry*
Inhibitory Concentration 50
Injections, Intravenous
Lung Neoplasms / drug therapy*
Lung Neoplasms / metabolism
Lung Neoplasms / pathology
Male
Mice, Inbred BALB C
Mice, Nude
Micelles
Paclitaxel / pharmacology
Quaternary Ammonium Compounds / chemistry*
Solubility
Surface Properties
Technology, Pharmaceutical / methods
Time Factors
Vitamin E / chemistry*
Xenograft Model Antitumor Assays

Substances

Antineoplastic Agents, Phytogenic
Drug Carriers
Flavonoids
Micelles
Quaternary Ammonium Compounds
baohuoside I
Vitamin E
Hyaluronic Acid
tocophersolan
Paclitaxel
didecyldimethylammonium