Biol. Pharm. Bull. 28(12) 2263—2267 (2005)

acidic polypeptide (molecular weight approximately 6900 Da), is one of the most potent inhibitors of thrombin and has proven to have outstanding anticoagulant and antithrombotic activities. Compared with other anticoagulant agents such as heparin, rHV possesses many advantages on safety, antigenicity and toxicity. Now rHV has been using for prophylaxis and treatment of heparin-induced thrombocytopenia (HIT), venous and arterial thrombosis, and shunt thrombosis or treatment of disseminated intravascular coagulation (DIC). Due to its polypeptide and hydrophilic nature, however, to date, rHV is usually given via parenteral injection (i.v. or s.c.) to assure efficient delivery of this drug. Unfortunately, in both cases, due to the inconvenience and associated side effects from injection such as local irritation. Its broader use has been limited by the lack of noninvasive delivery methods for this drug. Thus, the development of a convenient, noninvasive, alternative route of administration for rHV2 with comparable pharmacokinetic performance to parental injection would represent a significant advance in anticoagulant therapy. Compared to other non-injection administrations, such as oral formulation, nasal delivery is a much attractive route for its characteristics of avoiding liver first-pass effect, rapid on set action and a higher bioavailability. However, little attention has been paid to use nasal route as rHV delivery so far. Although nasal delivery possesses many advantages, protein and peptide drugs through the nasal route is still considerably less efficient than that of injectable route due mainly to intrinsic poor permeability and metabolism in nasal cavity. Scientists have made a lot of attempts to investigate the effective and well tolerated methods for improving the absorption of these bioactive peptides and proteins by nasal delivery. Among these approaches, using absorption enhancers still is the most simple and convenient means. Since the nasal epithelial cells which are joined by the tight junctions are dominant factor preventing hydrophilic macromolecules from permeability, it is important to study the uptake and transport mechanisms of these compounds for better understanding nasal permeability barrier, as well as the absorption of the proteins and peptides in nasal and the successful performance of delivery systems. Currently the related studies are still quite a few, in fact for most biologically active proteins and peptides, the absorption mechanisms in the nasal cavity have not been firmly established. The purpose of present study was to investigate the feasibility by nasal delivery of rHV2, as well as the possible absorption mechanisms of rHV2 across the nasal epithelium.