Hyaluronic acid derivative-coated nanohybrid liposomes for cancer imaging and drug delivery

• Published in: Journal of controlled release 2014-01, Vol.174, p.98-108
• Main Authors: Park, Ju-Hwan, Cho, Hyun-Jong, Yoon, Hong Yeol, Yoon, In-Soo, Ko, Seung-Hak, Shim, Jae-Seong, Cho, Jee-Hyun, Park, Jae Hyung, Kim, Kwangmeyung, Kwon, Ick Chan, Kim, Dae-Duk
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - blood; Antibiotics, Antineoplastic - chemistry; Antibiotics, Antineoplastic - pharmacokinetics; Cell Line, Tumor; Contrast Media - administration & dosage; Contrast Media - chemistry; Doxorubicin; Doxorubicin - administration & dosage; Doxorubicin - blood; Doxorubicin - chemistry; Doxorubicin - pharmacokinetics; Female; Gadolinium DTPA - administration & dosage; Gadolinium DTPA - chemistry; Humans; Hyaluronic Acid - chemistry; Hyaluronic acid–ceramide; Hybrid nanostructure; Lipid; Liposomes; Magnetic resonance imaging; Male; Mice; Mice, Nude; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Neoplasms - diagnosis; Neoplasms - drug therapy; Neoplasms - metabolism; Rats; Rats, Sprague-Dawley; Xenograft Model Antitumor Assays
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2013.11.016

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 120–130nm mean diameter and a narrow size distribution were developed. DOX release from the developed formulation was improved at acidic pH (pH5.5 and 6.8) versus physiological pH (pH7.4). 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. [Display omitted]