Rat nasal lavage biomarkers to assess preclinical irritation potential of nasal drug formulations and excipients.
J Pharm Sci
; 98(2): 495-502, 2009 Feb.
Article
em En
| MEDLINE
| ID: mdl-18506818
ABSTRACT
The goal of this study was to evaluate biomarkers of nasal mucosal damage for rapid assessment of irritancy potential of formulations in the rat nasal lavage model, a tool to facilitate nasal formulation development prior to histopathology studies. The nasal cavity of anesthetized rats was lavaged with normal saline 20 min pos-tdose. The collected fluid was analyzed for secreted total protein and biomarkers. Solutions tested include normal saline, buffers, benzalkonium chloride (BAC), lysophosphatidylcholine (LPC), and four marketed nasal products. Total protein, lactate dehydrogenase and interleukin-1alpha biomarkers were secreted to varying degrees. BAC (0.2%) and LPC (0.5%) exhibiting the strongest response with a signal window ranging from 3.4- to 87-fold greater levels than normal saline. Buffer treatments, excipients, and most marketed nasal products yielded levels similar to normal saline. There was a weak correlation between formulation osmolarity and surface tension with any of the biomarkers. Each nasal formulation elicited a unique protein and biomarker profile with total protein secretion correlated with IL-1alpha secretion suggesting the potential for an inflammatory response. Taken together, rapid and potentially mechanistic information on the preclinical acute irritancy potential of formulations was assessed in the rat nasal lavage model by benchmarking treatments relative to controls and marketed nasal products.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Biomarcadores
/
Proteínas
/
Testes de Toxicidade Aguda
/
Avaliação Pré-Clínica de Medicamentos
/
Excipientes
/
Irritantes
/
Mucosa Nasal
Tipo de estudo:
Evaluation_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Pharm Sci
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos