Folate-mediated poly(3-hydroxybutyrate-co-3-hydroxyoctanoate) nanoparticles for targeting drug delivery.
A novel targeting drug delivery system (TDDS) has been developed. Such a TDDS was prepared by W(1)/O/W(2) solvent extraction/evaporation method, adopting poly(3-hydroxybutyrate-co-3-hydroxyoctanoate) [P(HB-HO)] as the drug carrier, folic acid (FA) as the targeting ligand, and doxorubicin (DOX) as the model anticancer drug. The average size, drug loading capacity and encapsulation efficiency of the prepared DOX-loaded, folate-mediated P(HB-HO) nanoparticles (DOX/FA-PEG-P(HB-HO) NPs) were found to be around 240 nm, 29.6% and 83.5%. The in vitro release profile displayed that nearly 50% DOX was released in the first 5 days. The intracellular uptake tests of the nanoparticles (NPs) in vitro showed that the DOX/FA-PEG-P(HB-HO) NPs were more efficiently taken up by HeLa cells compared to non-folate-mediated P(HB-HO) NPs. In addition, DOX/FA-PEG-P(HB-HO) NPs (IC(50)=0.87 microM) showed greater cytotoxicity to HeLa cells than other treated groups. In vivo anti-tumor activity of the DOX/FA-PEG-P(HB-HO) NPs showed a much better therapeutic efficacy in inhibiting tumor growth, and the final mean tumor volume was 178.91+/-17.43 mm(3), significantly smaller than normal saline control group (542.58+/-45.19 mm(3)). All these results have illustrated that our techniques for the preparing of DOX/FA-PEG-P(HB-HO) NPs developed in present work are feasible and these NPs are effective in selective delivery of anticancer drug to the folate receptor-overexpressed cancer cells. The new TDDS may be a competent candidate in application in targeting treatment of cancers.
Zhang
Chan
C
Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan, PR China.
Zhao
Liangqi
L
Dong
Yuefeng
Y
Zhang
Xiaoyan
X
Lin
Ji
J
Chen
Zhang
Z
D020155:3-Hydroxybutyric Acid / Q000737:chemistry*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001692:Biological Transport; D002208:Caproates / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004317:Doxorubicin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D005492:Folic Acid / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D000094122:Polyhydroxybutyrates
D020155:3-Hydroxybutyric Acid; D000903:Antibiotics, Antineoplastic; D002208:Caproates; D004317:Doxorubicin; D004337:Drug Carriers; D005492:Folic Acid; C115940:poly(3-hydroxybutyrate-co-3-hydroxyhexanoate); D000094122:Polyhydroxybutyrates