한빛사 논문
Ju-Hwan Parka,1, Hyun-Jong Chob,1, Hong Yeol Yoonc, In-Soo Yoond, Seung-Hak Koe, Jae-Seong Shime,f, Jee-Hyun Chog, Jae Hyung Parkc, Kwangmeyung Kimh, Ick Chan Kwonh, Dae-Duk Kima,*
a College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea
b College of Pharmacy, Kangwon National University, Chuncheon 200-701, Republic of Korea
c Department of Polymer Science and Chemical Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea
d College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 534-729, Republic of Korea
e Biogenics Inc., Daejeon 305-510, Republic of Korea
f Skin & Tech Inc., Seongnam 461-713, Republic of Korea
g Division of Magnetic Resonance Research, Korea Basic Science Institute, Ochang 363-883, Republic of Korea
h Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 6, Seongbuk-gu, Seoul 136-791, Republic of Korea
*Corresponding author : Dae-Duk Kim
Abstract
Nanohybrid liposomes coated with amphiphilic hyaluronic acid–ceramide (HACE) was fabricated for targeted delivery of anticancer drug and in vivo cancer imaging. Nanohybrid liposomes including doxorubicin (DOX) and Magnevist, a contrast agent for magnetic resonance (MR) imaging, with 120–130 nm mean diameter and a narrow size distribution were developed. DOX release from the developed formulation was improved at acidic pH (pH 5.5 and 6.8) versus physiological pH (pH 7.4). Cytotoxicity induced by the blank plain liposome was reduced by coating the outer surface of the nanohybrid liposome with HACE. Cellular uptake of DOX from the nanohybrid liposome was enhanced by HA and CD44 receptor interaction, versus the plain liposome. In vivo contrast-enhancing effects revealed that the nanohybrid liposome can be used as a tumor targeting MR imaging probe for cancer diagnosis. In a pharmacokinetic study in rats, in vivo clearance of DOX was decreased in the order DOX solution, plain liposome (F2), and nanohybrid liposome (F3), indicating prolonged circulation of the drug in the blood stream and improved therapeutic efficacy of the nanohybrid liposome (F3). Based on these findings, the nanohybrid liposomal system may be a useful candidate for real-time cancer diagnosis and therapy.
Keywords
Doxorubicin; Hyaluronic acid–ceramide; Hybrid nanostructure; Lipid; Magnetic resonance imaging
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