Acta Pharmacologica Sinica (2010) 31: 237–243; doi: 10.1038/aps.2009.199

Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, China

Aim: 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 ¹²⁵I-Lf-PS and ¹²⁵I-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°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.

Conclusion: 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.

Keywords: blood-brain barrier; lactoferrin; transferrin; brain drug targeting