Pharmacological and Toxicity Profiles of Diverse Paclitaxel Preparations with Detoxifying Nanoformulations

Paclitaxel, a first-line chemotherapeutic agent widely used to treat a broad spectrum of solid malignancies, exerts potent antitumor activity by disrupting microtubule dynamics and arresting mitotic division of proliferating cancer cells. Its earliest marketed formulation utilizes Cremophor EL as a solubilizing excipient to overcome the poor aqueous solubility of paclitaxel. However, Cremophor EL is known to trigger severe adverse reactions, including acute hypersensitivity, peripheral neuropathy and leukopenia, greatly limiting the maximum safe administrable dose in clinical practice. To tackle these drawbacks, a variety of paclitaxel nanocarrier systems have been engineered to eliminate Cremophor EL. Such nanoformulations promote selective intratumoral drug accumulation relying on the enhanced permeability and retention (EPR) effect, effectively lowering excipient-related systemic toxicity. Although these strategies achieve encouraging therapeutic efficacy in preclinical animal investigations, the promising preclinical benefits cannot be fully recapitulated in subsequent clinical trials. Current paclitaxel nanoformulations still confront multiple unresolved hurdles, such as high manufacturing expenditure, intrinsic cytotoxicity of nanocarriers, latent chronic toxic risks and inadequate passive targeting efficiency. This article delineates paclitaxel's pharmacological mechanism, toxic features of conventional preparations, nanotechnology-enabled detoxification tactics, safety profiles, as well as persistent obstacles hindering further clinical translation.