Reformulating @entity73109 in XXXX Targeted Polymeric Nanoparticles Improves Its Therapeutic Index.

@entity1 @entity470 @entity19 @entity5 @entity149 @entity73109
Several promising anticancer drug candidates have been sidelined owing to their poor physicochemical properties or unfavorable pharmacokinetics, resulting in high overall cost of drug discovery and development. Use of alternative formulation strategies that alleviate these issues can help advance new molecules to the clinic at a significantly lower cost. @entity73109 is a natural product with potent anticancer activity. Its clinical trial was discontinued following the @entity149 . To improve the safety and potency of @entity73109 , we formulated the drug in polymeric nanoparticles targeted to the @entity470 ( @entity470 ) overexpressed on several types of @entity5 . Through in vitro studies in different @entity5 cell lines, we found that @entity470 targeted nanoparticles were significantly more effective in killing @entity5 cells than the free drug. In vivo pharmacokinetic studies revealed that encapsulation in nanoparticles resulted in lower brain penetration and enhanced @entity5 accumulation of the drug. Further, targeted nanoparticles were characterized by significantly enhanced @entity5 growth inhibitory activity in a @entity19 xenograft model of @entity5 . These results suggest that the therapeutic index of drugs that were previously considered unusable could be significantly improved by reformulation. Application of novel formulation strategies to previously abandoned drugs provides an opportunity to advance new molecules to the clinic at a lower cost. This can significantly increase the repertoire of treatment options available to @entity5 @entity1 .
