Effects of viscous hyaluronate-sodium solutions on the nasal absorption of vasopressin and an analogue

Pharm Res. 1991 Apr;8(4):471-4. doi: 10.1023/a:1015894910416.

Abstract

The effects of viscous solutions of hyaluronate-sodium of various average molecular weights (MW) on the nasal absorption of vasopressin (AVP) and its analogue, 1-deamino-8-D-arginine vasopressin (1-d-8-DAVP), were examined in rats. Solutions of hyaluronate with MW greater than 3 x 10(5) daltons enhanced the nasal absorption of AVP; solutions of MW 5.5 x 10(4) daltons were not effective. The enhancing effects on the nasal absorption of AVP and 1-d-8-DAVP were dependent on the concentration in the range of 0-1.5% (w/v) hyaluronate (MW 1.4 x 10(6) daltons). The nasal absorption of AVP was increased with this solution at lower pH. Bioavailabilities after nasal administration of AVP and 1-d-8-DAVP in hyaluronate solutions (MW 1.4 x 10(6) and 2 x 10(6) daltons) increased more than 2-and 1.6-fold as compared to nasal administration of AVP and 1-d-8-DAVP in buffer solutions (pH 7.0), respectively. Hyaluronate solution (MW 1.4 x 10(6) daltons) did not affect the ciliary beat frequency of rabbit nasal mucosal membranes in vitro. Therefore, hyaluronate solution may be useful as a vehicle for nasal delivery of AVP and 1-d-8-DAVP.

MeSH terms

  • Absorption / drug effects
  • Adhesiveness
  • Administration, Intranasal
  • Animals
  • Biological Availability
  • Deamino Arginine Vasopressin / administration & dosage
  • Deamino Arginine Vasopressin / pharmacokinetics*
  • Hyaluronic Acid / chemistry
  • Hyaluronic Acid / pharmacology*
  • In Vitro Techniques
  • Male
  • Mucociliary Clearance / drug effects
  • Nasal Mucosa / drug effects
  • Nasal Mucosa / metabolism*
  • Rabbits
  • Rats
  • Rats, Inbred Strains
  • Solutions
  • Vasopressins / administration & dosage
  • Vasopressins / pharmacokinetics*
  • Viscosity

Substances

  • Solutions
  • Vasopressins
  • Hyaluronic Acid
  • Deamino Arginine Vasopressin