Oral Bioavailability Enhancement in Anticancer Pharmacotherapy

Oral administration of anticancer agents offers distinct advantages in terms of patient convenience, adherence and healthcare resource utilisation compared with intravenous regimens. However, many chemotherapeutic and targeted therapies suffer from poor water solubility, limited membrane permeability and extensive hepatic first-pass metabolism, resulting in suboptimal systemic exposure. Over the past decade, a broad array of formulation and chemical strategies has been pursued to overcome these barriers. Approaches include the design of prodrugs that mask polar or bulky groups, enabling enhanced absorption and subsequent in vivo activation; incorporation of active ingredients into lipid-based systems such as self-emulsifying formulations, nanoemulsions and liposomes to improve dissolution and lymphatic uptake; and engineering of polymeric nanoparticles or micelles to modulate release kinetics and protect labile molecules. Co-crystal formation and solid dispersions have also been explored to alter crystal habit and enhance wettability. In parallel, the use of permeation enhancers, efflux transporter inhibitors and mucoadhesive excipients has shown promise in increasing intestinal uptake. Together, these innovations are expanding the therapeutic window of oral anticancer agents, facilitating maintenance dosing strategies and paving the way for more patient-centred care while aiming to maintain or enhance antitumour efficacy.

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Oral Bioavailability Enhancement in Anticancer Pharmacotherapy publication trend

The graph below shows the total number of articles in oral bioavailability enhancement in anticancer pharmacotherapy across all publications each year (not limited to Nature Index journals).

Technical terms

Oral bioavailability: The proportion of an orally administered dose that reaches systemic circulation in active form.

First-pass metabolism: The enzymatic transformation of a drug by the liver or gut wall before it reaches systemic circulation.

Prodrug: An inactive derivative that is metabolically converted into the active pharmacological agent after absorption.

Lipid-based formulation: A drug delivery system incorporating lipids to enhance solubility, stability and lymphatic uptake.

Nanoemulsion: A finely dispersed oil-in-water system with droplet sizes below 200 nm, used to improve drug dissolution and absorption.

Micelle: An aggregate of amphiphilic molecules in an aqueous environment that can encapsulate hydrophobic drugs to increase their apparent solubility.

References

1. Attempts to Improve Lipophilic Drugs’ Solubility and Bioavailability: A Focus on Fenretinide. Pharmaceutics (2024).
2. DHP23002 as a next generation oral paclitaxel formulation for pancreatic cancer therapy. PLOS ONE (2019).
3. IDN 5390: an oral taxane candidate for protracted treatment schedules. British Journal of Cancer (2003).