Quercetin-loaded freeze-dried nanomicelles: Improving absorption and anti-glioma efficiency in vitro and in vivo

• Published in: Journal of controlled release 2016-08, Vol.235, p.276-290
• Main Authors: Wang, Gang, Wang, Jun-Jie, Chen, Xuan-Li, Du, Li, Li, Fei
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; BBB; Blood-Brain Barrier - metabolism; Brain Neoplasms - drug therapy; Brain Neoplasms - pathology; Cell Line, Tumor; Cell Survival - drug effects; Delayed-Action Preparations - administration & dosage; Delayed-Action Preparations - pharmacology; Drug Delivery Systems; Drug Liberation; Freeze Drying; Freeze-dried; Glioma; Glioma - drug therapy; Glioma - pathology; Humans; Intestinal Absorption - drug effects; Mice, Inbred BALB C; Mice, Nude; Micelles; Nanomicelles; Nanoparticles - administration & dosage; Nanoparticles - therapeutic use; Quercetin; Quercetin - administration & dosage; Quercetin - pharmacokinetics; Quercetin - pharmacology; Quercetin - therapeutic use; Tumor Burden - drug effects
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2016.05.045

To improve its poor aqueous solubility and stability, the potential chemopreventive agent quercetin was encapsulated in freeze-dried polymeric micelles by a thin film hydration and vacuum freeze-drying process before being used for glioma chemotherapy. The micelle characteristics, release profile, cellular uptake, intracellular drug concentration, transport across the blood-brain barrier, and antitumor efficiency in vivo were investigated. Results showed that the particle size of quercetin-loaded freeze-dried nanomicelles (QUE-FD-NMs) ranged from 20 to 80nm, with an efficiently sustained release profile. Increased intracellular uptake into Caco-2 cells with low cytotoxicity, efficient penetration of BBB, and powerful cytotoxicity on C6 glioma cells were observed. QUE-FD-NMs accumulated in tumor-bearing brain tissues and exhibited significant antitumor effects in vivo, which significantly benefited the survival of glioma-bearing mice. These findings suggest that freeze-drying micelles loaded with quercetin is a promising drug delivery method for glioma therapy. A novel drug delivery system for the treatment of glioma was developed. Quercetin-loaded freeze-dried nanomicelles (QUE-FD-NMs) significantly increased cellular uptake of quercetin into Caco-2 cells with low cytotoxicity, effective penetration of the blood-brain barrier, and powerful cytotoxicity on C6 glioma cells. Furthermore, QUE-FD-NMs exhibited significant anti-tumor effects in vivo, providing significant survival benefit. Therefore, freeze-dried nanomicelles loaded with quercetin are a promising drug delivery system for targeting brain tumors, particularly glioma. [Display omitted] •Quercetin loaded freeze-dried micelles with sustained release profile, increased cellular uptake.•QUE-FD-NMs efficiently deliver QUE to accumulate in primary tumor tissues.•QUE-FD-NMs exhibit the better survival rate and the inhibited tumor growth in vivo.•Freeze-drying micelles loaded with quercetin is a promising drug delivery for glioma therapy.