Overview of intranasally delivered peptides: key considerations for pharmaceutical development.

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.