Effect of a Drug Delivery System Made of Quercetin Formulated into PEGylation Liposomes on Cervical Carcinoma In Vitro and In Vivo
Jian Li, Zhen Li, Yanting Gao, Shihe Liu, Kun Li, Shuai Wang, Liming Gao, Ming Shi, Zhiwei Liu, Zengsheng Han, Yan Qiu
Abstract
Quercetin is a well-known flavonoid for its potent antitumor and antiproliferative effects on a wide range of human cancer cell lines. However, the delivery of quercetin is challenging due to its extreme insolubility in water. The intention of this study was to evaluate the antitumor effect of quercetin-loaded PEGylated liposomes (PEG-Que-NLs) in vitro and in vivo. We first prepared PEG-Que-NLs by method of thin film hydration; further determined, the optimum ratios of quercetin to Soybean phosphatidylcholine (SPC), to cholesterol (CHL), and to PEG-4000 were 1 : 8, 1 : 2, and 1 : 2 ( <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" id="M1"> <a:mi>w</a:mi> <a:mo>/</a:mo> <a:mi>w</a:mi> </a:math> ), respectively, and the optimal hydration temperature was 55°C when the mean vesicle diameter and apparent Zeta potential of PEG-Que-NLs were found to be <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" id="M2"> <c:mn>171.3</c:mn> <c:mo>±</c:mo> <c:mn>10.4</c:mn> </c:math> nm and <e:math xmlns:e="http://www.w3.org/1998/Math/MathML" id="M3"> <e:mo>−</e:mo> <e:mn>13.1</e:mn> <e:mo>±</e:mo> <e:mn>2.1</e:mn> </e:math> mV, respectively; the encapsulation efficiency and the drug loading of PEG-Que-NLs were <g:math xmlns:g="http://www.w3.org/1998/Math/MathML" id="M4"> <g:mn>81.25</g:mn> <g:mo>±</g:mo> <g:mn>3.12</g:mn> <g:mi>%</g:mi> </g:math> and <i:math xmlns:i="http://www.w3.org/1998/Math/MathML" id="M5"> <i:mn>8.5</i:mn> <i:mo>±</i:mo> <i:mn>0.77</i:mn> <i:mi>%</i:mi> </i:math> , respectively. Drug release study in vitro showed that PEG-Que-NLs exhibited a slow-release effect without significant burst effect. Furthermore, the inhibition effect of PEG-Que-NLs on HeLa cells was considerably higher than free quercetin (free-Que) and quercetin liposomes (Que-NLs). Intravenous injection of PEG-Que-NLs into U14 bearing mouse models inhibited the cervical carcinoma growth significantly, and the tumor inhibition rate was much higher than free-Que and Que-NLs. These results of this study indicated that PEG-Que-NLs exhibited potential application prospects in the treatment of malignant tumors because of its tumor targeting, slow-release properties, and the solubility improvement of quercetin.