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Papers Published

1. Saha, S; Banskota, S; Yousefpour, P; Schaal, JL; Zakharov, N; Liu, J; Dzuricky, M; He, Z; Roberts, S; Li, X; Chilkoti, A, Preclinical Development of a Genetically Engineered Albumin-Binding Nanoparticle of Paclitaxel, Small Science, vol. 4 no. 11 (November, 2024) [doi] .
   (last updated on 2025/04/17)

   Abstract:
   Nab-paclitaxel (Abraxane), an albumin-bound solvent-free paclitaxel (PTX) formulation that takes advantage of the endogenous albumin transport pathway, is the current gold standard for treatment of solid tumors with PTX. However, nab-paclitaxel has several limitations, including complex manufacturing, immunogenicity, slow drug-release, and a narrow therapeutic window. Nevertheless, no other PTX formulation has gained the Food and Drug Administration approval since Abraxane's 18-year reign. Addressing these concerns, herein, a PTX-loaded nanoparticle of a recombinant polypeptide that—like nab-paclitaxel—capitalizes on the long in vivo half-life of albumin is reported. This genetically engineered nanoparticle packages PTX in the core of the nanoparticle and displays an albumin-binding domain on the exterior of the nanoparticle. Upon in vivo administration, the drug-loaded nanoparticle binds albumin with nanomolar affinity, and acquires an albumin-corona, which eliminates the need to use exogenous albumin. The nanoparticles can be stored at subzero temperature as lyophilized powder without any cryoprotectants for upto a year and can be reconstituted on-demand in aqueous buffer at high concentration, thus greatly simplifying formulation processes. These albumin-binding nanoparticles improve the therapeutic window by at least twofold compared to nonalbumin-binding counterpart and outperform nab-paclitaxel in multiple murine tumor models, results that have been independently replicated by a contract research organization.