Targeted delivery of curcumin to tumors via PEG-derivatized FTS-based micellar system.
Curcumin and S-trans, trans-farnesylthiosalicylic acid (FTS) are two promising anticancer agents. In this study, we demonstrated that the two agents exerted significant synergy in antitumor activity in various types of cancer cells with combination indices ranging from 0.46 to 0.98 (a value of less than unity indicates synergism). We have further shown that synergistic-targeted co-delivery of the two agents can be achieved via formulating curcumin in polyethylene glycol (PEG)-derivatized FTS-based nanomicellar system. Curcumin formulated in PEG-FTS micelles had small size of around 20 nm. The nanomicellar curcumin demonstrated enhanced cytotoxicity towards several cancer cell lines in vitro. Intravenous application of curcumin-loaded micelle (20 mg kg(-1) curcumin) led to a significantly more effective inhibition of tumor growth in a syngeneic mouse breast cancer model (4T1.2) than curcumin formulated in Cremophor/EL (P < 0.05).
Center for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, 639 Salk Hall, Pittsburgh, PA, 15261, USA.
Yichao
Y
Chen
Xiaolan
X
Zhang
Jianqin
J
Lu
Yixian
Y
Huang
Jiang
J
Li
Song
S
Li
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage; D016503:Drug Delivery Systems; D005204:Farnesol / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D016328:NF-kappa B / Q000187:drug effects; D011092:Polyethylene Glycols; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects; D012459:Salicylates / Q000008:administration & dosage; D015398:Signal Transduction / Q000187:drug effects
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D008823:Micelles; D016328:NF-kappa B; D012459:Salicylates; C093323:farnesylthiosalicylic acid; D011092:Polyethylene Glycols; D005204:Farnesol; D051057:Proto-Oncogene Proteins c-akt; D003474:Curcumin