title: Effects of low-viscosity sodium hyaluronate preparation on the pulmonary absorption of rh-insulin in rats.
abstract: OBJECTIVE
  A low-viscosity formulation for pulmonary delivery of rh-insulin as model peptide drugs was developed using a solution of sodium hyaluronate.
  
  
  METHODS
  The effects of different concentrations and pH values of low-viscosity solutions of hyaluronate on the pulmonary absorption of rh-insulin were examined after intratracheal administration in rats. The permeation of fluorescein isothiocyanate (FITC)-dextran (molecular weight 4300; FD-4) and insulin through excised rat trachea in vitro were also examined.
  
  
  RESULTS
  The hyaluronate (2140 kDa) solutions (0.1% and 0.2% w/v) at pH 7.0 significantly enhanced the pharmacological availability (PAB) of insulin compared to the aqueous solution of insulin at pH 7.0. The absorption-enhancing effect at a concentration of 0.1% w/v hyaluronate was greater than that at a concentration of 0.2% w/v hyaluronate. Furthermore, the greatest absorption-enhancing effect was obtained, regardless of the molecular weight of hyaluronate, when the concentration of hyaluronate was adjusted to 0.47 microM. Absorption-enhancing effects were consistent with the effect of a 0.1 w/v hyaluronate preparation at pH 4.0 and 7.0 on the permeation of FITC-dextran and insulin through excised rat trachea in vitro.
  
  
  CONCLUSIONS
  Low-viscosity hyaluronate preparation was shown to be a useful vehicle for pulmonary delivery of peptide drugs.
authors: Department of Pharmaceutics, Hokkaido College of Pharmacy, Otaru-city, Japan. morimoto@hokuyakudai.ac.jp
authors: K
authors: K
authors: Morimoto
authors: K
authors: K
authors: Metsugi
authors: H
authors: H
authors: Katsumata
authors: K
authors: K
authors: Iwanaga
authors: M
authors: M
authors: Kakemi
mesh_terms: D000042:Absorption; D000276:Adjuvants, Immunologic / Q000737:chemistry*; D000818:Animals; D001682:Biological Availability; D016503:Drug Delivery Systems; D006820:Hyaluronic Acid / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics*; D007328:Insulin / Q000493:pharmacokinetics*; D008168:Lung / Q000187:drug effects; D008297:Male; D008970:Molecular Weight; D051381:Rats; D017208:Rats, Wistar; D014783:Viscosity
chemical_list: D000276:Adjuvants, Immunologic; D007004:Hypoglycemic Agents; D007328:Insulin; D006820:Hyaluronic Acid