Targeted Drug Delivery Systems for Enhanced Oral Absorption

The oral route offers the most convenient and acceptable means of drug administration, yet it is beset by barriers that limit the bioavailability of many therapeutics. Enzymatic degradation, low solubility, variable gastric pH and first-pass metabolism combine to restrict the fraction of an administered dose that reaches systemic circulation. Targeted drug delivery systems seek to overcome these challenges by exploiting physiological transport pathways and novel materials. Strategies include the development of prodrugs linked to endogenous substrates, surface-modified nanoparticles that engage specific intestinal transporters, and formulation with permeability enhancers to transiently modulate mucosal barriers. Advances in nanotechnology have enabled the design of vehicles such as liposomes and polymeric nanoparticles with tailored surface chemistries—PEGylation, ligand conjugation or responsive coatings—to achieve site-specific absorption and controlled release. By co-opting transport proteins of the solute carrier family, delivery systems can be directed across the intestinal epithelium, while pH-sensitive encapsulation and enteric coatings protect labile molecules from gastric degradation. Collectively, these approaches aim to boost oral bioavailability, reduce therapeutic dose and improve patient adherence, with applications spanning antivirals, anticancer agents and peptides that would otherwise require parenteral delivery.

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Targeted Drug Delivery Systems for Enhanced Oral Absorption publication trend

The graph below shows the total number of articles in targeted drug delivery systems for enhanced oral absorption across all publications each year (not limited to Nature Index journals).

Technical terms

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

Prodrug: An inactive or less active derivative of a drug designed to undergo in vivo transformation to release the active compound.

Solute carrier (SLC) transporters: A superfamily of membrane proteins that mediate uptake of nutrients and xenobiotics across cell membranes.

Liposomes: Spherical vesicles composed of phospholipid bilayers used to encapsulate therapeutic agents.

PEGylation: Attachment of polyethylene glycol chains to molecules or particles to improve stability and circulation time.

Permeability enhancers: Formulation additives that transiently increase epithelial barrier permeability to aid drug absorption.

Oligopeptide transporter 1 (PepT1): An intestinal proton-coupled transporter that facilitates uptake of di- and tri-peptides and certain peptide-like drugs.

References

1. Transporter-Guided Delivery of Nanoparticles to Improve Drug Permeation across Cellular Barriers and Drug Exposure to Selective Cell Types. Frontiers in Pharmacology (2018).
2. Transporter-Mediated Drug Delivery. Molecules (2023).
3. Transporter-Targeted Nano-Sized Vehicles for Enhanced and Site-Specific Drug Delivery. Cancers (2020).
4. Permeability Enhancers Dramatically Increase Zanamivir Absolute Bioavailability in Rats: Implications for an Orally Bioavailable Influenza Treatment. PLOS ONE (2013).
5. Thiodipeptides targeting the intestinal oligopeptide transporter as a general approach to improving oral drug delivery. European Journal of Medicinal Chemistry (2018).