Uptake of ANG1005, a novel paclitaxel derivative, through the blood-brain barrier into brain and experimental brain metastases of breast cancer

Pharm Res. 2009 Nov;26(11):2486-94. doi: 10.1007/s11095-009-9964-5. Epub 2009 Sep 23.


Purpose: We evaluated the uptake of angiopep-2 paclitaxel conjugate, ANG1005, into brain and brain metastases of breast cancer in rodents. Most anticancer drugs show poor delivery to brain tumors due to limited transport across the blood-brain barrier (BBB). To overcome this, a 19-amino acid peptide (angiopep-2) was developed that binds to low density lipoprotein receptor-related protein (LRP) receptors at the BBB and has the potential to deliver drugs to brain by receptor-mediated transport.

Methods: The transfer coefficient (K(in)) for brain influx was measured by in situ rat brain perfusion. Drug distribution was determined at 30 min after i.v. injection in mice bearing intracerebral MDA-MB-231BR metastases of breast cancer.

Results: The BBB K(in) for (125)I-ANG1005 uptake (7.3 +/- 0.2 x 10(-3) mL/s/g) exceeded that for (3)H-paclitaxel (8.5 +/- 0.5 x 10(-5)) by 86-fold. Over 70% of (125)I-ANG1005 tracer stayed in brain after capillary depletion or vascular washout. Brain (125)I-ANG1005 uptake was reduced by unlabeled angiopep-2 vector and by LRP ligands, consistent with receptor transport. In vivo uptake of (125)I-ANG1005 into vascularly corrected brain and brain metastases exceeded that of (14)C-paclitaxel by 4-54-fold.

Conclusions: The results demonstrate that ANG1005 shows significantly improved delivery to brain and brain metastases of breast cancer compared to free paclitaxel.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacokinetics*
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Blood-Brain Barrier / metabolism*
  • Brain Neoplasms / drug therapy
  • Breast Neoplasms / drug therapy
  • Chromatography, High Pressure Liquid
  • Female
  • Mice
  • Mice, Nude
  • Paclitaxel / analogs & derivatives*
  • Paclitaxel / pharmacokinetics
  • Paclitaxel / pharmacology
  • Peptides
  • Rats


  • Antineoplastic Agents, Phytogenic
  • Peptides
  • paclitaxel-Angiopep-2 conjugate
  • Paclitaxel