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.

A novel method for strict intranasal delivery of non-replicating RSV vaccines in cotton rats and non-human primates.

Respiratory syncytial virus (RSV) is the most common viral cause of bronchiolitis and pneumonia in children twelve months of age or younger and a significant cause of lower respiratory disease in older adults. As various clinical and preclinical candidates advance, cotton rats (Sigmodon hispidus) and non-human primates (NHP) continue to play a valuable role in RSV vaccine development, since both animals are semi-permissive to human RSV (HRSV). However, appropriate utilization of the models is critical to avoid mis-interpretation of the preclinical findings. Using a multimodality imaging approach; a fluorescence based optical imaging technique for the cotton rat and a nuclear medicine based positron emission tomography (PET) imaging technique for monkeys, we demonstrate that many common practices for intranasal immunization in both species result in inoculum delivery to the lower respiratory tract, which can result in poor translation of outcomes from the preclinical to the clinical setting. Using these technologies we define a method to limit the distribution of intranasally administered vaccines solely to the upper airway of each species, which includes volume restrictions in combination with injectable anesthesia. We show using our newly defined methods for strict intranasal immunization that these methods impact the immune responses and efficacy observed when compared to vaccination methods resulting in distribution to both the upper and lower respiratory tracts. These data emphasize the importance of well-characterized immunization methods in the preclinical assessment of intranasally delivered vaccine candidates.