Pharmacokinetics of oral therapeutics delivered by dendrimer-based carriers

ABSTRACT

Introduction: Dendrimers showed promise as carriers for oral delivery due to their nanoscale size and transepithelial permeability across the gut epithelium. However, for the successful approval of dendrimer-based oral therapeutics for human use, it is essential to understand their pharmacokinetics. The knowledge of pharmacokinetics of drugs delivered with dendrimers within the context of oral delivery of therapeutics will help in the design of clinical trials, and development of dosage regimens.

Areas covered: This review summarizes the pharmacokinetic aspects of dendrimer and dendrimer-drug complexes after oral administration. We discussed the influence of size, core chemistry, surface charge, surface chemistry, and modification on the pharmacokinetics of dendrimers and dendrimer-drug complexes. Furthermore, we also discussed studies involving alternative dosage forms such as matrix tablets containing dendrimers, dendrimers encapsulated in lipid nanostructures, and chitosan anchored-dendrimers.

Expert opinion: From the studies, it is evident that dendrimers significantly improve the oral bioavailability of drugs with poor biopharmaceutical properties. However, further in vivo studies are needed to establish the relationship between the properties of dendrimers and oral pharmacokinetics of dendrimer-drug complexes and conjugates.

KEYWORDS:

• Bioavailability
• clearance
• dendrimers
• gastric mucosa
• half-life
• nanotechnology
• opsonization
• pharmacokinetic

Article highlights

• Dendrimers have shown potential to be carriers for oral drug delivery.

• Pharmacokinetics of dendrimers after oral delivery is dependent on size, charge, and surface moiety.

• Dendrimers were shown to improve the bioavailability of drugs with poor biopharmaceutical properties.

• Future studies must involve a detailed pharmacokinetic evaluation of dendrimers after oral administration in various species.

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.

Reviewer disclosures

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

Additional information

Funding

This paper was partially supported by a grant from the National Institutes of Health (R01ES024681).