Effects of Viscous Hyaluronate–Sodium Solutions on the Nasal Absorption of Vasopressin and An Analogue

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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, l-deamino-8-D-arginine vasopressin (l-d-8-DAVP), were examined in rats. Solutions of hyaluronate with MW greater than 3 × 105 daltons enhanced the nasal absorption of AVP; solutions of MW 5.5 × 104 daltons were not effective. The enhancing effects on the nasal absorption of AVP and l-d-8-DAVP were dependent on the concentration in the range of 0–1.5% (w/v) hyaluronate (MW 1.4 × 106 daltons). The nasal absorption of AVP was increased with this solution at lower pH. Bioavailabilities after nasal administration of AVP and l-d-8-DAVP in hyaluronate solutions (MW 1.4 × 106 and 2 × 106 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 × 106 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 l-d-8-DAVP.

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