Current Perspectives on Paclitaxel: Focus on Its Production, Delivery and Combination Therapy.

Abstract

Paclitaxel is an anticancer drug first isolated from the bark of the Pacific yew tree. It has been widely used for the treatment of ovarian, breast, uterine and other cancers because of its low toxicity, high efficiency and broad-spectrum anticancer activity, and it is considered to be one of the most successful natural anticancer drugs available. Paclitaxel is a microtubule-targeting drug whose main molecular mechanism is to disrupt microtubule dynamics and induce mitotic arrest and cell death. Despite the many clinical successes of paclitaxel, the extraction of natural paclitaxel from Taxus species has proven to be environmentally unsustainable and economically unviable. As a result, researchers are constantly working to find innovative ways to meet society's need for this drug. Currently, many methods, including artificial cultivation, microbial fermentation, chemical synthesis, and tissue and cell culture, have been explored and developed to obtain paclitaxel. In addition, the poor water solubility of paclitaxel has led to significant limitations in its clinical application. Conventional paclitaxel formulations use Cremophor EL and ethanol to dissolve paclitaxel, which can lead to serious side effects. In recent decades, a series of new nanotechnology-based paclitaxel dosage forms have been developed, including albumin-bound paclitaxel, polymeric micellar paclitaxel, polymer-paclitaxel couples, and liposome-encapsulated paclitaxel. These nanoformulations can significantly reduce the toxicity of paclitaxel and greatly improve its anti-tumor efficiency. This paper reviews the development of the production, dosage form and combination therapy of paclitaxel in recent years and presents an outlook, with the aim of providing a theoretical basis and reference for further research on the production and application of paclitaxel in the future.