重组水蛭素-2脂质体的制备及大鼠鼻腔给药药代动力学

目的：为了提高重组水蛭素-2(rHV2)鼻腔给药的生物利用度,研制rHV2脂质体并对其理化性质和大鼠经鼻给药后药代动力学特点进行研究。方法：以逆相蒸发法制备rHV2脂质体；通过研究rHV2脂质体的包封率、粒径、稳定性来考察其理化性质；将制备的rHV2脂质体鼻腔给予大鼠,用呈色肽法测定不同时间血浆中rHV2的浓度,通过3p87程序拟合药代动力学参数。结果：用该法制备的脂质体包封率约为76.95%,平均粒径为168.3 nm,分布在24～286 nm,相对峰宽±0.47,稳定性较好；药代动力学研究表明,rHV2脂质体较rHV2生理盐水溶液的鼻腔吸收明显增加。结论：将rHV2制备成脂质体可明显增加鼻腔给药的生物利用度。

Studies on preparation of recombinant hirudin-2 liposome and its pharmacokinetics by nasal delivery in rats

Objective: To promote the nasal absorption of recombinant hirudin-2, the preparation and physicochemical properties of recombinant hirudin-2 liposomes, as well as its pharmacokinetic characteristics and bioavailability in rats after nasal administration were investigated. Method: Recombinant hirudin-2 liposomes were prepared by reversal phase evaporation; the test of physicochemical properties including encapsulation efficiency, particle size and stability of liposome suspensions were determined by HPLC; Recombinant hirudin-2 concentration in plasma was determined by chromogenic substrate method and the relative bioavailability and pharmacokinetic parameters were also calculated using software program 3p87. Result: The encapsulation efficiency of recombinant hirudin-2 liposome reached greater than 76.95%,with an average particle size of about 168.3 nm, size distribution ranging from 24 to 286 nm, relative peak width of ±0.47, and a good stability. Conclusion: Compared with recombinant hirudin-2 solution, liposome preparation enhanced the nasal absorption of recombinant hirudin-2.