Nanocarriers for delivery of taxanes: A review on physicochemical and biological aspects

Paclitaxel (PTX), Docetaxel (DTX) and Cabazitaxel (CTX) are taxanes: substances that belong to a class of diterpenes derived from plants of the Taxus genus (yew). Taxanes are currently used in clinical practice for the treatment of various types of cancer, including breast, ovarian, lung, and prostate, among others. Despite their wide applications, taxanes have some disadvantages that can hinder their use as a chemotheraputic, including low solubility, high toxicity and induction of multidrug resistance (MDR). To circumvent the low solubility of PTX, the commercial formulation Taxol® contains Cremophor EL® (polyethoxylated castor oil) and dehydrated alcohol at a 1:1 ratio to solubilize the drug, but the excipient has toxic effects. In this context, we will discuss how nanotechnology contributes to improving the therapeutic efficacy of taxanes by promoting increased solubility after nanoencapsulation and allowing for co-delivery of taxanes with other chemotherapeutics and/or substances with antitumor potential. Nanosystrems may present passive accumulation of taxanes in cancerous tissues through the increased permeability and retention effect (EPR), thus enhancing therapeutic efficacy in experimental models in vitro and in vivo. In this article, we will present and discuss some conventional nanosystems including: lipid nanoparticles (liposomes, solid lipid nanoparticles, nanostructured lipid carriers and nanoemulsions), polymeric nanoparticles (albumin, chitosan, poly lactic-co-glycolic acid, poly ε-caprolactone and other polymers) and inorganic nanoparticles (gold, iron and silver), in addition to site-specific drug delivery through the use of nanoparticles conjugated with monoclonal antibodies, peptides, folate and transferrin. Physicochemical aspects (particle size, zeta potential, encapsulation efficiency) and biological aspects (cytotoxicity, cellular uptake, in vivo efficacy) of taxane-loaded nanoparticles will be commented on. Next, we will discuss nanosystems that can respond to physical and chemical stimuli in the tumor microenvironment. It is noteworthy that the successes in nanosystem and, more specifically, nanoencapsulation research of taxanes resulted in FDA approval of a PTX-linked albumin nanosystem, Abraxane®, in 2005. Finally, several clinical studies have been developed in recent years demonstrating advances and therapeutic benefit, proving the potential of nanocarriers to increase the effectiveness of chemotherapy with taxanes.