The role of membrane transporters in the absorption of atrazine following nasal exposure.

OBJECTIVE: The purpose of these studies was to investigate the uptake of atrazine across the nasal mucosa to determine whether direct transport to the brain through the olfactory epithelium is likely to occur. These studies were undertaken to provide important new information about the potential for the enhanced neurotoxicity of herbicides following nasal inhalation. MATERIALS AND METHODS: Transport of atrazine from aqueous solution and from commercial atrazine-containing herbicide products was assessed using excised nasal mucosal tissues. The permeation rate and the role of membrane transporters in the uptake of atrazine across the nasal mucosa were also investigated. Histological examination of the nasal tissues was conducted to assess the effects of commercial atrazine-containing products on nasal tissue morphology. RESULTS: Atrazine showed high flux across both nasal respiratory and olfactory tissues, and efflux transporters were found to play an essential role in limiting its uptake at low exposure concentrations. Commercial atrazine-containing herbicide products showed remarkably high transfer across the nasal tissues, and histological evaluation showed significant changes in the morphology of the nasal epithelium following exposure to the herbicide products. DISCUSSION: Lipophilic herbicides such as atrazine can freely permeate across the nasal mucosa despite the activity of efflux transporters. The adjuvant compounds in commercial herbicide products disrupt the nasal mucosa's epithelial barrier, resulting in even greater atrazine permeation across the tissues. The properties of the herbicide itself and those of the formulated products play crucial roles in the potential for the enhanced neurotoxicity of herbicides following nasal inhalation.

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.