Bile acids and bile acid derivatives: use in drug delivery systems and as therapeutic agents

ABSTRACT

Introduction: Bile acids are biological surfactants and signaling molecules with important paracrine and endocrine functions. The enterohepatic organotropism of bile acids turns these facial amphiphiles into attractive drug delivery systems for selective drug targeting to the liver or to enhance drug bioavailability by improving intestinal absorption and metabolic stability.

Areas covered: Bile acid-based amphiphiles, in the form of mixed micelles, bilosomes, drug conjugates and hybrid lipid-polymer nanoparticles are critically discussed as delivery systems for anticancer drugs, antimicrobial agents and therapeutic peptides/proteins, including vaccines. Therapeutic applications of bile acid derivatives as cytotoxic and neuroprotective agents are also addressed.

Expert opinion: Bile acids play an important role in modulating cancer therapy and novel derivatives with cytotoxic activity not restricted to the gastrointestinal tract can be expected. Selective toxicity targeting the bacterial membrane remains an attractive area of research for further development of bile acid-based bactericidal agents. On the other hand, the neuroprotective properties of some bile acids offer therapeutic potential in neurodegenerative disorders. Bile acid-based nanoparticles are also a growing research area due to the unique characteristics and tunable properties of these nanosystems. Therefore, multifaceted pharmaceutical and biomedical applications of bile salts are to be expected in the near future.

KEYWORDS:

• Antimicrobial agents
• bile acids
• bilosomes
• cancer
• drug delivery
• micelles
• nanoparticles
• neuroprotection

Article highlights

• Bile acids are facial amphiphiles and important signaling molecules with enterohepatic organotropism that can be exploited in prodrug design or to improve oral absorption and metabolic stability of poorly water-soluble drugs and hydrophilic therapeutic macromolecules.

• Bile acid-based drug delivery systems, in the form of mixed micelles, bilosomes and drug conjugates are versatile nanocarriers that have recently been optimized by conjugation with hydrophilic polymers leading to size-tunable bile acid-based nanoparticles.

• The cytotoxic properties of hydrophobic bile acids have been exploited in the development of novel drugs for cancer chemotherapy, and several bile acid derivatives show impressive anti-proliferative activities against a wide variety of human cancer cell lines not restricted to the gastrointestinal tract, including breast, prostate, cervical, colon and liver cancer cells.

• The anti-apoptotic properties of the hydrophilic bile acids have expanded to other apoptotic-related conditions beyond liver diseases and their neuroprotective effects have been demonstrated in several neurodegenerative disorders, including Alzheimer’s disease, and also in prion disease.

• Cationic bile acid-based amphiphiles, which mimic cationic antimicrobial peptides, are broad-spectrum bactericidal agents that target the bacterial membrane, and selective bactericidal activity can been achieved by modulation of the charged head groups.

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Declaration of interest

The author has 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.