Degradation of recombinant hirudin-2 in nasal mucosa of rabbits in vitro / 药学学报

ABSTRACT

<p><b>AIM</b>To investigate the degradation of recombinant hirudin-2 (rHV2) in nasal mucosa of rabbit.</p><p><b>METHODS</b>The specific and accurate HPLC method was developed for analyzing rHV2; The degrading ratios of rHV2 at different concentrations and at pH conditions in rabbit nasal mucosa homogenate were determined; The results in nasal mucosa homogenate were compared with that in small intestinal mucosa homogenate of rabbits. The stability of rHV2 in the enzyme extract of nasal mucosa surface and the effect of proteolysis inhibitor bacitracin on the degradation of rHV2 in nasal mucosa homogenate were also estimated.</p><p><b>RESULTS</b>The degradation of rHV2 in rabbit nasal mucosa homogenate showed concentration- and pH-dependence; rHV2 in nasal mucosa homogenate was more stable than that in intestinal mucosa homogenate. Also rHV2 was more stable in the enzyme extracts of nasal serosal surface than that of mucosa surface. Addition of bacitracin was able to inhibit the degradation to some degree.</p><p><b>CONCLUSION</b>Comparing with oral administration, rHV2 nasal delivery was a more tolerant route.</p>