Colorectal cancer management: strategies in drug delivery

ABSTRACT

Introduction

Colorectal cancer (CRC) is the third most common cancer leading to death worldwide following breast and lung cancer with the incidence rate of 10%. The treatment comprises surgery, radiation, and ablation therapy depending upon the stage of cancer.

Areas covered

The review focuses on various drug delivery strategies explored to circumvent the major constraints associated with the conventional drug delivery systems—poor bioavailability, intra- and inter individual variability, exposure of normal cells to antineoplastic agents, and presence of efflux pump. All these attributes impact the effective delivery of chemotherapeutic agents at the tumor site. The various target specific drug delivery systems developed for colorectal cancer include pH-dependent, microbiologically triggered, time-dependent, magnetically driven, pressure-dependent, prodrug/polysaccharide-based, osmotic and ligand-mediated systems. This review enumerates novel target specific approaches developed and investigated for potential utility in CRC therapeutics.

Expert opinion

The limitations of conventional delivery systems can be overcome by the development of colon-specific targeted drug delivery systems that overcome the obstacles of nonspecific biodistribution, drug resistance, and unwanted adverse effects of conventional drug delivery systems. In addition, nanotechnology approaches help to increase drug solubility, bioavailability, reduce side effects, and provide superior drug response in CRC.

Graphical abstract

KEYWORDS:

• Colon cancer
• drug targeting
• site specific delivery
• tumor targeting
• chemotherapeutics and nanotechnology

Article highlights

• Colorectal cancer is one of the deadliest diseases globally owing to lack of early detection methods and appropriate drug delivery strategies.

• Targeted therapy impacting the Wnt/β-catenin, Notch, Hedgehog, and TGF-β /SMAD, PI3K/AKT or RAS/RAF is a rapidly emerging research area in colorectal cancer therapeutics.

• Colon targeted delivery systems exploiting the physiological properties of the colon: specific pH, varied bacterial microflora, fluid content, and receptors specifically expressed in the colon influence the clinical outcomes in colorectal cancer.

• Combination therapeutics formulated as novel nanotech delivery systems extend the survival and quality of life in patients.

• Synthetic and nature-derived anticancer agents alone and in combination are in various phases of clinical trials for colorectal cancer.

This box summarizes key points contained in the article.

Acknowledgments

The authors acknowledge the technical support rendered by Ms. Palak Jethva, SVKM’s Dr. Bhanuben Nanavati College of Pharmacy for doing the figures in this manuscript.

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.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.