Effect of lactoferrin- and transferrin-conjugated polymersomes in brain targeting: in vitro and in vivo evaluations.
OBJECTIVE
To evaluate the effect of lactoferrin (Lf) and transferrin (Tf) in brain targeting.


METHODS
Polymersomes (PSs), employed as vectors, were conjugated with Lf or Tf and were characterized by morphology, particle size, zeta potential, and surface densities of the Lf or Tf molecules. In vitro uptake of Lf-PS and Tf-PS by bEnd.3 cells was investigated using coumarin-6 as a fluorescent probe. In vivo tissue distribution and pharmacokinetics of (125)I-Lf-PS and (125)I-Tf-PS were also examined.


RESULTS
The mean particle size of PS, Lf-PS, and Tf-PS was around 150 nm and the zeta potential of the PSs was about -20 mV. Less than 0.12% of the coumarin was released from coumarin-6-loaded PS in 84 h indicating that coumarin-6 was an accurate probe for the PSs' behavior in vitro. It was shown that the uptake of Lf-PS and Tf-PS by bEnd.3 cells was time-, temperature-, and concentration-dependent. Both Lf and Tf could increase the cell uptake of PSs at 37 degrees C, but the uptake of Tf-PS was significantly greater than that of Lf-PS. In vivo tissue distribution and pharmacokinetics in mice revealed higher brain uptake and distribution of Tf-PS than Lf-PS, which was in accordance with in vitro uptake results. The drug targeting index (DTI) of Tf-PS with regard to Lf-PS was 1.51.


CONCLUSIONS
Using a PS as the delivery vector and bEnd.3 cells as the model of the blood-brain barrier (BBB), Tf was more effective than Lf in brain targeting.
Department of Pharmaceutics, Fudan University, Shanghai, China.
Hui-le
HL
Gao
Zhi-qing
ZQ
Pang
Li
L
Fan
Kai-li
KL
Hu
Bing-xian
BX
Wu
Xin-guo
XG
Jiang
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D016503:Drug Delivery Systems; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D007781:Lactoferrin / Q000493:pharmacokinetics / Q000494:pharmacology*; D051379:Mice; D010316:Particle Size; D014018:Tissue Distribution; D014168:Transferrin / Q000493:pharmacokinetics / Q000494:pharmacology*
D007457:Iodine Radioisotopes; D014168:Transferrin; D007781:Lactoferrin