Overview of intranasally delivered peptides: key considerations for pharmaceutical development

ABSTRACT

Introduction: Intranasal (IN) delivery for peptides provides unique advantages compared to other invasive systemic delivery routes. However, there still lacks a clear understanding on how to evaluate the potential of the peptides for nasal delivery and key considerations for the nasal formulation development.

Areas covered: A retrospective analysis of intranasally delivered peptides was conducted. The goals of this undertaking were 1) to build a database of the key physicochemical and pharmacokinetic properties of peptides delivered by the nasal route, 2) to evaluate formulation attributes applied to IN peptide delivery systems, and 3) to provide key considerations for IN delivery of peptides.

Expert Opinion/Commentary: Extensive data mining showed that peptides with molecular weights up to 6000 Da have been delivered intranasally. The high solubility of some peptides highlighted the possibility of delivering sufficient amounts of peptide in the limited volume available for nasal sprays. Permeation enhancers and mucoadhesives have shown promise in improving the IN bioavailability of peptides. Other formulation considerations, such as the type of formulation, pH, osmolality, as well as drug deposition, are reviewed herein. Based on this retrospective analysis, key considerations for nasal peptides formulations were proposed to guide drug discovery and development for IN delivery of peptides.

KEYWORDS:

• Bioavailability
• formulation
• intranasal drug delivery
• molecular weight
• nasal saturation capacity
• peptides
• pharmacokinetics
• solubility

Article highlights

• ‘Most currently marketed intranasal peptide formulations have low bioavailabilities, generally less than 5%, in humans’

• ‘The mechanism of absorption of peptides across the nasal mucosa is not fully understood, but appears to involve both paracellular and endocytotoic routes’

• ‘High peptide solubilities provide the possibility of administering large doses in the limited volume available for nasal spray’

• ‘Peptides administered intranasally have a comparable onset of action to other parenteral/injectable routes of administration’

• ‘Inclusion of permeation enhancers in intranasal peptide formulations may result in a significant increase in bioavailability’

• ‘Peptide molecules with molecular weights up to 6000 Da have been delivered across the human nasal mucosa’

Acknowledgments

The authors would like to thank Mallory Stenslik, Adrian Goodey, and Nancy Agrawal for their reviews that contributed to this manuscript.

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 Declarations

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

Additional information

Funding

This paper was not funded.