Oral delivery of peptide therapeutics in infants: Challenges and opportunities

Abstract

The vast majority of drugs are not designed or developed for pediatric and infant populations. Peptide drugs, which have become increasingly relevant in the past several decades, are no exception. Unfortunately, nearly all of the 60+ approved peptide drugs are formulated for injection, a particularly unfriendly mode of administration for infants. Although three peptide drugs were recently approved for oral formulations, this major advance in peptide drug delivery is available only for adults. In this review, we consider the current challenges and opportunities for the oral formulation of peptide therapeutics, specifically for infant populations. We describe the strategies that enable oral protein delivery and the potential impact of infant physiology on those strategies. We also detail the limited but encouraging progress towards 1) adapting conventional drug development and delivery approaches to infants and 2) designing novel infant-centric formulations. Together, these efforts underscore the feasibility of oral peptide delivery in infants and provide motivation to increase attention paid to this underserved area of drug delivery and formulation.

Keywords: Dosage forms; Infant therapy; Oral delivery; Pediatrics; Peptides; Protein delivery.

Fig. 1 –

The physiological barriers to delivering oral macromolecular drugs in infants differ from adults.

Fig. 2 –

The stomach and small intestine present unique biochemical and physical barriers to the oral delivery of peptide therapeutics.

Fig. 3 –

The complex mucus matrix and the intestinal epithelium pose transport barriers to the oral absorption of peptide therapeutics. A drug must diffuse through the intestinal mucus and then permeate the epithelial monolayer to reach systemic circulation. Transport across the epithelium can occur passively (via the transcellular or paracellular route) or actively (by transcytosis or receptor-mediated uptake).