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首页> 外文期刊>Journal of Microencapsulation: Microcapsules Liposomes Nanoparticles Microcells Microspheres >Delivery of rSLPI in a liposomal carrier for inhalation provides protection against cathepsin L degradation
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Delivery of rSLPI in a liposomal carrier for inhalation provides protection against cathepsin L degradation

机译：将rSLPI递送至脂质体载体中进行吸入可防止组织蛋白酶L降解

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摘要

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: Choi 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.
机译：分泌型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，可保护肺部免受炎症过程中释放的白细胞蛋白酶引起的过度组织损伤。重组SLPI（rSLPI）已显示出潜在的治疗炎症性肺部疾病的潜力。迄今为止，其临床应用受到组织蛋白酶的快速酶促裂解和吸入后迅速从肺中清除的限制。在这项研究中，rSLPI被封装在1,2-二油酰基-sn-甘油3- [磷酸-L-丝氨酸]：胆固醇（DOPS：Chol）脂质体中进行吸入。将rSLPI与组织蛋白酶L孵育会导致活性完全丧失，而将rSLPI封装在DOPS中：Choi脂质体在用组织蛋白酶L攻击后保留了其活性的92.6％。使用标准的雾化器有效地雾化了装载了rSLPI的脂质体，而活性损失最小和稳定性。该制剂具有生物相容性，在体外细胞培养研究中，封装似乎并未减少对细胞内作用位点的访问。因此，rSLPI的脂质体封装可提高稳定性，并可能降低吸入后达到治疗效果所需的剂量水平和给药频率。

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