Abstract 2063: Trojan horsing the blood-brain barrier with nanocarriers aided by adenosine receptor agonists

Abstract

Abstract Drug delivery to the central nervous system (CNS) is not easy compared to other body systems due to the presence of the blood brain barrier (BBB). It is essential that any delivery system to the CNS needs to be efficient and non-toxic. These features are fulfilled through tailored nanomicelles, non cross-linked and disulfide cross-linked micelles (NCM and DCM, respectively) and Polyvinyl alcohol-based polymeric nanoparticles. It has recently been reported that adenosine receptor agonists can modulate the permeability of the BBB. For example 5′-(N-Ethylcarboxamido)Adenosine (NECA) helps increase penetrability of the BBB membrane to macromolecules. We were able to demonstrate that similar strategy can be applied in mouse model for facilitating the penetration of NCM, DCM, and PVA-nanoparticles through the BBB. In the murine model we found that NECA stimulated the uptake of these nanoparticles to organs expressing adenosine receptors, especially the brain. DCM and NCM uptake was not seen in the brain without prior administration of NECA. NECA has been previously shown to alter tight junction adhesion molecules (Occludin) expressed on brain endothelial cells. NECA at 5.3 mg/kg best facilitated the penetration of both DCM and NCM at an optimal loading dosage of 33 mg/kg. NECA opened the BBB and facilitated the penetration of nanoparticles through the BBB at a constant rate. This allows potential for future drug-loading studies on a diverse scale for chemotherapeutics, kinase inhibitors, and other drug classes. Note: This abstract was not presented at the meeting. Citation Format: Nasir Al Awwad. Trojan horsing the blood-brain barrier with nanocarriers aided by adenosine receptor agonists. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2063. doi:10.1158/1538-7445.AM2014-2063