Hyaluronic acid conjugated albumin nanoparticles for efficient receptor mediated brain targeted delivery of temozolomide

Abstract

In the present investigation, temozolomide (TMZ) loaded albumin nanoparticles (TNPs) were prepared by desolvation method and optimized by Box-Behnken design. Hyaluronic acid (HA) was used to modify the surface of TNPs to achieve CD44 receptor mediated targeting (HA-TNPs). The developed nanoparticles were characterized and evaluated using various in vitro and in vivo techniques. HA-TNPs were able to cross the blood brain barrier (BBB) as demonstrated in BBB passage study performed on monolayer and co-culture models. Cell viability assay demonstrated superior suppression of growth of U87 MG cells by HA-TNPs as compared to pure drug. HA-TNPs were able to generate reactive oxygen species (ROS) in U87 MG cells and their uptake was both endocytosis mediated (caveolae pathway) and CD44 receptor mediated as confirmed by CD44 receptor blocking study. In vivo results showed improvement in pharmacokinetics of TMZ as significant enhancement in plasma AUC, t1/2 and MRT from HA-TNPs was observed as compared to TMZ alone. Biodistribution results demonstrated higher accumulation of TMZ in brain and significant decrease of drug in other vital organs like liver and lungs by HA-TNPs as compared to pure drug. From all these results, it was concluded that HA-TNPs have potential to target brain tumor more specifically as compared to pure TMZ and may act as a promising targeted delivery platform.