Nanoparticulated docetaxel exerts enhanced anticancer efficacy and overcomes existing limitations of traditional drugs

Abstract

Nanoparticulation of insoluble drugs improves dissolution rate, resulting in increased bioavailability that leads to increased stability, better efficacy, and reduced toxicity of drugs. Docetaxel (DTX), under the trade name Taxotere™, is one of the representative anticancer chemotherapeutic agents of this era. However, this highly lipophilic and insoluble drug has many adverse effects. Our novel and widely applicable nanoparticulation using fat and supercritical fluid (NUFS™) technology enabled successful nanoscale particulation of DTX (Nufs-DTX). Nufs-DTX showed enhanced dissolution rate and increased aqueous stability in water. After confirming the preserved mechanism of action of DTX, which targets microtubules, we showed that Nufs-DTX exhibited similar effects in proliferation and clonogenic assays using A549 cells. Interestingly, we observed that Nufs-DTX had a greater in vivo tumor growth delay effect on an A549 xenograft model than Taxotere™, which was in agreement with the improved drug accumulation in tumors according to the biodistribution result, and was caused by the enhanced permeability and retention (EPR) effect. Although both Nufs-DTX and Taxotere™ showed negative results for our administration dose in the hematologic toxicity test, Nufs-DTX showed much less toxicity than Taxotere™ in edema, paralysis, and paw-withdrawal latency on a hot plate analysis that are regarded as indicators of fluid retention, peripheral neuropathy, and thermal threshold, respectively, for toxicological tests. In summary, compared with Taxotere™, Nufs-DTX, which was generated by our new platform technology using lipid, supercritical fluid, and carbon dioxide (CO 2 ), maintained its biochemical properties as a cytotoxic agent and had better tumor targeting ability, better in vivo therapeutic effect, and less toxicity, thereby overcoming the current hurdles of traditional drugs.

Chrysin Increases the Therapeutic Efficacy of Docetaxel and Mitigates Docetaxel-Induced Edema

“…The DTX-induced edema model was established in our previous study. 26 To elucidate the effect of chrysin on DTX-induced edema, chrysin was orally administered 2 hours before DTX treatment. Paw edema was measured before and after drug treatment.…”

Progress in the chemotherapeutic treatment of osteosarcoma (Review)

“…Certain scholars have reported that TXT can inhibit the proliferation of OS cells and induce apoptosis, and that such inhibition is time-and dose-dependent (48,49). Combination therapy using TXT and gemcitabine (GEM) has also been reported to enhance antitumor effects (50,51). A number of scholars (52) have used chemotherapy-related drug target gene detection via the application of second-generation high-throughput sequencing technology in patients with OS undergoing surgical resection.…”

Co-delivery of paclitaxel and TOS-cisplatin via TAT-targeted solid lipid nanoparticles with synergistic antitumor activity against cervical cancer

“…This phenomenon may be explained by the fact that solid tumors have leaky micro-vasculatures and the nano-sized particles could passively target the tumor due to the enhanced permeability and retention (EPR) effects. 55 The EPR effects prevented the entry of the system into the normal cell but favored selective entry into the tumor, which resulted in the efficient drug accumulation in tumor tissue. Specific distribution of the drug in the tumor tissue compared with the other tissues could decrease the side effects and lead to better antitumor therapeutic efficiency.…”