2′-Behenoyl-paclitaxel conjugate containing lipid nanoparticles for the treatment of metastatic breast cancer

The aim of these studies was to develop a novel 2′-behenoyl-paclitaxel (C22-PX) conjugate nanoparticle (NP) formulation for the treatment of metastatic breast cancer. A lipophilic paclitaxel derivative C22-PX was synthesized and incorporated into lipid-based NPs. Free C22-PX and its NP formulation were evaluated in a series of in vitro and in vivo studies. The results demonstrated that C22-PX NPs were much better tolerated and had significantly higher plasma and tumor AUCs compared to Taxol at the maximum tolerated dose (MTD) in a subcutaneous 4T1 mouse mammary carcinoma model. These benefits resulted in significantly improved antitumor efficacy with the NP-based formulation.

• Lipophilic paclitaxel derivative for increased affinity and retention in lipid-based nanoparticles.
• Improved pharmacokinetic, biodistribution, and tumor accumulation profile with lipid-based nanoparticles versus Taxol.
• Improved maximum tolerated dose with lipid-based nanoparticles versus Taxol.
• Improved anti-tumor efficacy with lipid-based nanoparticles versus Taxol in a 4T1 mouse mammary carcinoma model.