Current advances in development of new docetaxel formulations

ABSTRACT

Introduction: Docetaxel (DTX) is one of the most important chemotherapeutic agents and has been widely used for treatment of various types of cancers. However, the clinical chemotherapy of DTX gives many undesirable side effects due to the usage of organic solvent in the injection and its low selectivity for tumor cells. With the evolution of pharmaceutical technologies, great efforts have been paid to develop new DTX formulations to overcome these problems.

Areas covered: This review provided an overview of the preparation and activities of new DTX formulations, which were classified by administration methods, including injection, oral, transdermal and rectal administration. Besides, up to date information of the clinical status of new DTX formulations was summarized. We also discussed the challenges and perspectives of the future development of DTX formulations.

Expert opinion: There have been numerous studies on new DTX-based formulations in recent years, and many of them exhibited significantly enhanced anti-tumor and targeting activity compared with DTX in preclinical studies. However, only a few entered clinical trials, and none has been approved into market. The clinical translation of experimental drug faces many hurdles, including the limited knowledge of nanomedicine and oncology, safety issues, controllable and reproducible production.

KEYWORDS:

• Docetaxel
• drug delivery system
• targeting
• liposome
• nanoparticle

Article highlights

• Currently, docetaxel is an indispensable chemotherapeutic agent in treatment of a variety of cancers. However, the usage of organic solvent in docetaxel formulation and its low selective distribution cause many severe side effects.

• The administration methods of new docetaxel formulations are not limited to injection, which also include oral, transdermal, and rectal administrations.

• Nano-delivery systems account for the vast majority of newly designed docetaxel formulations, including liposomes, polymeric nanoparticles or micelles, polymer-drug conjugates, dendrimers, nanosuspensions, and nanoemulsions.

• The nano-delivery systems improve the aqueous solubility of docetaxel and enhance its targeting ability through both passive and active targeting strategies, which subsequently increases the anti-tumor efficacy and avoided sides effects on normal tissues.

• Some novel nano-delivery systems co-delivering multiple therapeutic agents (e.g., siRNA or other anti-tumor drugs) with docetaxel have been investigated. The combination strategy exhibits synergistical anti-tumor effects via various mechanisms.

• There are still many problems that baffle the translation of preclinically effective docetaxel formulations into clinic trials and market, such as shortage of knowledge in nanomedicine and oncotherapy, safety and production issues.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work is supported by National Key R&D Program of China (2018YFC0311305); Special projects of Foshan science and technology innovation team (2017IT100054).