School of Pharmacy, Royal College of Surgeons in Ireland, Dublin, Ireland.
J Microencapsul. 2009 Sep;26(6):513-22. doi: 10.1080/02652040802466535.
Secretory leukocyte protease inhibitor (SLPI) is an endogenous serine protease inhibitor that protects the lungs from excessive tissue damage caused by leukocyte proteases released during inflammation. Recombinant SLPI (rSLPI) has shown potential as a treatment for inflammatory lung conditions. To date, its clinical application has been limited by rapid enzymatic cleavage by cathepsins and rapid clearance from the lungs after inhalation. In this study, rSLPI was encapsulated in 1,2-Dioleoyl-sn-Glycero-3-[Phospho-L-Serine] : Cholesterol (DOPS : Chol) liposomes for inhalation. Incubation of rSLPI with cathepsin L leads to complete loss of activity while encapsulation of rSLPI in DOPS : Chol liposomes retained 92.6% of its activity after challenge with cathepsin L. rSLPI-loaded liposomes were aerosolized efficiently using a standard nebulizer with a minimal loss of activity and stability. This formulation was biocompatible and encapsulation did not appear to diminish access to intracellular sites of action in in vitro cell culture studies. Liposome encapsulation of rSLPI therefore improves stability and potentially reduces the level and frequency of dosing required for therapeutic effect after inhalation.
分泌白细胞蛋白酶抑制剂（SLPI）是一种内源性丝氨酸蛋白酶抑制剂，可防止肺部因白细胞蛋白酶在炎症期间释放而导致过度的组织损伤。重组 SLPI（rSLPI）已显示出作为治疗炎症性肺病的潜力。迄今为止，其临床应用受到组织蛋白酶快速酶切和吸入后肺部快速清除的限制。在这项研究中，rSLPI 被包裹在 1,2-二油酰基-sn-甘油-3-[磷酸-L-丝氨酸]：胆固醇（DOPS：胆固醇）脂质体中用于吸入。rSLPI 与组织蛋白酶 L 孵育会导致完全失活，而将 rSLPI 包裹在 DOPS：胆固醇脂质体中，在受到组织蛋白酶 L 挑战后仍保留其 92.6%的活性。使用标准雾化器可有效地将 rSLPI 负载的脂质体雾化，而活性和稳定性的损失最小。该配方具有生物相容性，并且包封似乎不会减少细胞内作用部位的可及性，在体外细胞培养研究中。因此，rSLPI 的脂质体包封可提高稳定性，并可能减少吸入治疗所需的剂量水平和频率。
