Cationic albumin conjugated pegylated nanoparticle with its transcytosis ability and little toxicity against blood-brain barrier

Int J Pharm. 2005 May 13;295(1-2):247-60. doi: 10.1016/j.ijpharm.2005.01.043.

Abstract

Our newly developed drug delivery carrier, cationic bovine serum albumin (CBSA) conjugated with poly(ethyleneglycol)-poly(lactide) (PEG-PLA) nanoparticle (CBSA-NP), was designed for brain drug delivery. CBSA, as a brain specific targetor, was covalently conjugated with the maleimide function group at the distal of poly(ethyleneglycol) (PEG) surrounding the nanoparticles. To evaluate its blood-brain barrier (BBB) transcytosis and toxicity against the BBB endothelial tight junction, we have explored a method of coculture with brain capillary endothelial cells (BCECs) on the top of micro-porous membrane of cell culture insert and astrocytes on the bottom side. The permeability of 14C-labeled sucrose was determined. For the CBSA-NP transcytosis study, a lipophilic fluorescent probe, 6-coumarin, was incorporated into nanoparticles. The BBB permeability of CBSA-NP in vitro was calculated and compared with native bovine serum albumin (BSA) conjugated pegylated nanoparticles (BSA-NP). As the coculture model, the transendothelial electrical resistance reached up to 313+/-23 ohms cm2. The tight junction between BCECs in the coculture could be visualized by scanning electron microscopy and transmission electron microscopy. The unchanged permeability of 14C-labeled sucrose comparing to that in the appearance of 200 microg/ml of CBSA-NP proved that CBSA-NP did not impact the integrity of BBB endothelial tight junctions. CBSA-NP also showed little toxicity against BCECs. The permeability of CBSA-NP was about 7.76 times higher than that of BSA-NP, while the transcytosis was inhibited in the excess of free CBSA. It was concluded that CBSA-NP preferentially transported across BBB with little toxicity, which offered the possibility to deliver therapeutic agents to CNS.

MeSH terms

  • Animals
  • Astrocytes / metabolism
  • Biological Transport
  • Blood-Brain Barrier*
  • Cattle
  • Cells, Cultured
  • Coculture Techniques
  • Drug Carriers*
  • Endothelial Cells / metabolism
  • Nanostructures*
  • Polyethylene Glycols / administration & dosage*
  • Rats
  • Rats, Sprague-Dawley
  • Serum Albumin, Bovine / administration & dosage*
  • Tight Junctions / physiology

Substances

  • Drug Carriers
  • Serum Albumin, Bovine
  • Polyethylene Glycols