Transferrin-conjugated lipid-coated PLGA nanoparticles for targeted delivery of aromatase inhibitor 7alpha-APTADD to breast cancer cells.
Transferrin (Tf)-conjugated lipid-coated poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles carrying the aromatase inhibitor, 7alpha-(4'-amino)phenylthio-1,4-androstadiene-3,17-dione (7alpha-APTADD), were synthesized by a solvent injection method. Formulation parameters including PLGA-to-lipid, egg PC-to-TPGS, and drug-to-PLGA ratios and aqueous-to-organic phase ratio at the point of synthesis were optimized to obtain nanoparticles with desired sizes and drug loading efficiency. The optimal formulation had a drug loading efficiency of 36.3+/-3.4%, mean diameter of 170.3+/-7.6nm and zeta potential of -18.9+/-1.5mV. The aromatase inhibition activity of the nanoparticles was evaluated in SKBR-3 breast cancer cells. IC(50) value of the Tf-nanoparticles was ranging from 0.77 to 1.21nM, and IC(50) value of the nanoparticles was ranging from 1.90 to 3.41nM (n=3). The former is significantly lower than the latter (p<0.05). These results suggested that the aromatase inhibition activity of the Tf-nanoparticles was enhanced relative to that of the non-targeted nanoparticles, which was attributable to Tf receptor (TfR) mediated uptake. In conclusion, Tf-conjugated lipid-coated PLGA nanoparticles are potential vehicles for improving the efficiency and specificity of therapeutic delivery of aromatase inhibitors.
Division of Pharmaceutics, College of Pharmacy, Ohio State University, Columbus, OH 43210, USA.
Yu
Y
Zheng
Bo
B
Yu
Wanlop
W
Weecharangsan
Longzhu
L
Piao
Michael
M
Darby
Yicheng
Y
Mao
Rumiana
R
Koynova
Xiaojuan
X
Yang
Hong
H
Li
Songlin
S
Xu
L James
LJ
Lee
Yasuro
Y
Sugimoto
Robert W
RW
Brueggemeier
Robert J
RJ
Lee
D000735:Androstenedione / Q000008:administration & dosage / Q000031:analogs & derivatives*; D047072:Aromatase Inhibitors / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000138:chemical synthesis / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D053758:Nanoparticles / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D055672:Static Electricity; D014168:Transferrin / Q000008:administration & dosage* / Q000737:chemistry
D047072:Aromatase Inhibitors; D004337:Drug Carriers; D014168:Transferrin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000735:Androstenedione; C028626:7-(4'-amino)phenylthioandrostenedione