Lim Grace J, Ishiuji Yozo, Dawn Aerlyn, Harrison Benjamin, Kim Do Won, Atala Anthony, Yosipovitch Gil
1Institute for Regenerative Medicine, 2Departments of Dermatology, Neurobiology & Anatomy, Wake Forest University School of Medicine, Winston-Salem, USA.
Acta Derm Venereol. 2008;88(4):327-30. doi: 10.2340/00015555-0480.
As yet no transdermal topical formulations have been developed for the treatment of chronic itch. We developed a formulation containing 2 mg butorphanol tartrate in 100 microl purified water encapsulated into multilamellar phospholipid vesicles. Drug permeation experiments were studied with Franz diffusion chambers using human skin in vitro and on rat skin in vivo. Histological analysis of rat skins was performed to evaluate skin irritation of the formulation in vivo. Physical properties showed stable formulation with desirable viscosity. In vitro dermal penetration rate data suggest that there was significant permeation at time-points 2 h and 4 h, and a steady state was achieved afterwards to 24 h. Maximal plasma butorphanol concentration was noted at 2 h and steady state was achieved at 8 h. Visual skin assessment as well as histological analysis of excised rat skin did not demonstrate any evidence of inflammation and irritation. In vitro and in vivo analysis demonstrated release of a consistent amount of butorphanol in a sustained manner for 24 h. This liposomal transdermal delivery formulation could serve as a method to deliver butorphanol for patients with chronic pruritus.
迄今为止，尚未开发出用于治疗慢性瘙痒的透皮局部用制剂。我们研发了一种制剂，其在100微升纯水中含有2毫克酒石酸布托啡诺，封装于多层磷脂囊泡中。使用Franz扩散池，在体外用人皮肤以及在体内用大鼠皮肤进行了药物渗透实验。对大鼠皮肤进行组织学分析，以评估该制剂在体内的皮肤刺激性。物理性质表明该制剂稳定且具有理想的粘度。体外皮肤渗透速率数据表明，在2小时和4小时的时间点有显著渗透，之后至24小时达到稳态。在2小时时观察到血浆布托啡诺浓度最高，在8小时时达到稳态。对切除的大鼠皮肤进行的视觉皮肤评估以及组织学分析均未显示任何炎症和刺激迹象。体外和体内分析表明，布托啡诺以持续方式释放出恒定的量达24小时。这种脂质体透皮给药制剂可作为一种为慢性瘙痒患者递送布托啡诺的方法。
