Application of nanocarriers for paclitaxel delivery and chemotherapy of cancer

Paclitaxel (PTX) is one of the most efficacious and frequently used drugs for treating ovarian, breast, non-small lung, head, neck and urological cancers and Kaposi’s sarcoma. Paclitaxel is a lipophilic compound with a log P value of 3.96 and has very low aqueous solubility (<  0.01mg/mL) and no ionizable functional groups posing difficulties in its delivery. Taxol® (PTX formulation with Cremophor EL®) has been shown to be efficacious in treating certain types of cancer. However, its therapeutic use is limited due to dose-dependent toxicities, such as peripheral neuropathy, hypotension and hypersensitivity and the induction of multi-drug resistance. A preferable substitute for Taxol® is Abraxane® (PTX bound to albumin). Although cancer patients have a better overall therapeutic response rate to Abraxane® (33%) than Taxol® (19%), further improvements in its efficacy and safety can be achieved with a nanocarrier-based drug delivery system. The formulation of PTX, in combination with nanocarriers, produces (1) sustained delivery of high concentrations of anti-cancer drugs; (2) passive targeting of tumors via an increase in enhanced permeability and retention (EPR) effect; (3) prevention of drug biotransformation in the circulation; and (4) a decrease in the magnitude and severity of toxic effects. In this book chapter several PTX nanocarrier drug delivery systems such as nanoparticles, liposomes, dendrimers, micelles, nanotubes, niosomes, proniosomes, ethosomes, microparticles and carbon dots for treating various cancer types are discussed. This chapter also highlights the possibilities and challenges of nanocarriers for the effective delivery of PTX and their role in overcoming resistance to PTX.