PARENT SESSION
1:30 PM to 3:30 PM
Tuesday, April 23, 2002
Poster Session 21 Radiation-Drug Interaction
Room: Nevada Exhibition Center

(P26-272) Targeting drug delivery carriers to irradiated tissue .

Haybert, Jean^*,1, Dalal, Milind², Chen, Xin¹, Yuan, Hong¹, Goetz, Douglas², Kiani, Mohammad¹, ¹ School of Biomedical Engineering and Department of Radiation Oncology, University of Tennessee Health Science Center, Memphis, TN² Department of Chemical Engineering, Ohio University, Athens, OH

ABSTRACT-
Microvasculature that is exposed to ionizing radiation is significantly transformed. One of the changes that take place is the up-regulation of adhesion molecules on the lumenal surface of the endothelium. This phenomenon can be exploited to aid in the development of a system which targets drugs to tissue that has already been irradiated as a part of therapeutic treatment. We used polystyrene microspheres (model drug carriers) coated with the mAbs to specific adhesion molecules (ICAM-1 and E-selectin) present on the surface of irradiated (10 Gy gamma radiation; 4 Gy/min) human umbilical vein endothelial cells (HUVEC). Under shear flow conditions (1.5 dynes/cm2) the number of adherent anti-ICAM-1 microspheres on irradiated HUVEC was up to 4.5 +/- 0.9 times (P < 0.01) that of control. These ratios could be enhanced by increasing the density of the mAbs on the surface of the microspheres, adding red blood cells to the suspending media or by reducing shear stress. In a rat closed cranial window in vivo model the number of adherent anti-ICAM-1 microspheres in irradiated cerebral tissue was 3.2 +/- 1.2 times that of control (un-irradiated) tissues at 24 hours post-irradiation. Forty-eight hours post-irradiation, the number of adherent anti-ICAM-1 microspheres increased to 6.5 +/- 1.8 times that of control cranial tissue. These results show that model drug carriers bearing mAbs to inducible endothelial cell adhesion molecules preferentially bind to irradiated microvasculature both in vitro and in vivo thereby suggesting that targeted drug delivery could be achieved using this technique. We are currently developing PEGylated biodegradable particles ligated with mAbs to E-selectin and ICAM-1 for use in this targeted delivery scheme. (Funded by NSF Grant BES0090009 (MFK/DJG) and an Individual Grant from The Whitaker Foundation (DJG)).

KEYWORDS: targeted drug delivery, adhesion molecule, radiation therapy, microcirculation