Abstract
Paclitaxel is one of the most effective chemotherapeutic drugs ever developed and is active against a broad range of cancers, such as lung, ovarian, and breast cancers. Due to its low water solubility, paclitaxel is formulated in a mixture of Cremophor EL and dehydrated ethanol (50:50, v/v) a combination known as Taxol. However, Taxol has some severe side effects related to Cremophor EL and ethanol. Therefore, there is an urgent need for the development of alternative Taxol formulations. The encapsulation of paclitaxel in biodegradable and non-toxic nano-delivery systems can protect the drug from degradation during circulation and in-turn protect the body from toxic side effects of the drug thereby lowering its toxicity, increasing its circulation half-life, exhibiting improved pharmacokinetic profiles, and demonstrating better patient compliance. Also, nanoparticle-based delivery systems can take advantage of the enhanced permeability and retention (EPR) effect for passive tumor targeting, therefore, they are promising carriers to improve the therapeutic index and decrease the side effects of paclitaxel. To date, paclitaxel albumin-bound nanoparticles (Abraxane®) have been approved by the FDA for the treatment of metastatic breast cancer and non-small cell lung cancer (NSCLC). In addition, there are a number of novel paclitaxel nanoparticle formulations in clinical trials. In this comprehensive review, several types of developed paclitaxel nano-delivery systems will be covered and discussed, such as polymeric nanoparticles, lipid-based formulations, polymer conjugates, inorganic nanoparticles, carbon nanotubes, nanocrystals, and cyclodextrin nanoparticles.
Highlights
Paclitaxel is one of the most effective chemotherapeutic drugs ever developed and is active against a broad range of cancers, such as lung, ovarian, and breast cancers
They are small in size, which enables the preferential delivery of PX into the tumor site due to the enhanced permeability and retention (EPR) effect
The current Taxol formulations have issues related to the use of Cremophor EL and ethanol
Summary
Paclitaxel (PX), isolated from the bark of Pacific Yew (Taxus brevifolia), which was first discovered by Mrs Monroe E. PX is a substrate of P-glycoprotein (P-gp), which actively pumps PX out of the cells and induces drug resistance [4] To overcome this problem, several P-gp inhibitors, such as verapamil [5] and PSC 833 [6], were co-administered with Taxol but the results were disappointing due to their toxicity and/or alteration of PX pharmacokinetics and biodistribution. Abraxane®, a PX albuminbound NP formulation with the particle size of ~130 nm, was approved by the FDA in 2005 for the treatment of metastatic breast cancer. This formulation had demonstrated some advantages in terms of reduced toxicity compared to Taxol.
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