Luo Zhilin, Ji Liyuan, Liu Hongting, Sun Yao, Zhao Conglu, Xu Xiang, Gu Xiaoting, Ai Xiaoyu, Yang Cheng
College of Pharmacy, Nankai University, No. 38 Tongyan Road, Haihe Education Park, Jinnan District, Tianjin, 300350, China.
Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China.
AAPS PharmSciTech. 2023 Nov 16;24(8):235. doi: 10.1208/s12249-023-02690-w.
Idiopathic pulmonary fibrosis (IPF) is a progressive, fibrotic interstitial lung disease with unclear etiology and increasing prevalence. Pulmonary administration can make the drug directly reach the lung lesion location and reduce systemic toxic and side effects. The effectiveness of lenalidomide (Len) liposomal lung delivery in idiopathic pulmonary fibrosis was investigated. Len liposomes (Len-Lip) were prepared from soybean lecithin, cholesterol (Chol), and medicine in different weight ratios by thin film hydration method. The Len-Lip were spherical in shape with an average size of 226.7 ± 1.389 nm. The liposomes with a higher negative zeta potential of around - 34 mV, which was conducive to improving stability by repelling each other. The drug loading and encapsulation rate were 2.42 ± 0.07% and 85.47 ± 2.42%. Len-Lip had little toxicity at the cellular level and were well taken up by cells. At bleomycin-induced pulmonary fibrosis model mice, inhalation Len-Lip could improve lung function and decrease lung hydroxyproline contents, and alleviate pulmonary fibrosis state. Inhalation Len-Lip provided a reference for the treatment of idiopathic pulmonary fibrosis.
特发性肺纤维化(IPF)是一种病因不明、患病率不断上升的进行性纤维化间质性肺疾病。肺部给药可使药物直接到达肺部病变部位,减少全身毒副作用。研究了来那度胺(Len)脂质体肺部给药治疗特发性肺纤维化的有效性。采用薄膜水化法,以不同重量比的大豆卵磷脂、胆固醇(Chol)和药物制备Len脂质体(Len-Lip)。Len-Lip呈球形,平均粒径为226.7±1.389nm。脂质体具有较高的负zeta电位,约为-34mV,有利于通过相互排斥提高稳定性。载药量和包封率分别为2.42±0.07%和85.47±2.42%。Len-Lip在细胞水平上毒性较小,且能被细胞良好摄取。在博来霉素诱导的肺纤维化模型小鼠中,吸入Len-Lip可改善肺功能,降低肺羟脯氨酸含量,减轻肺纤维化状态。吸入Len-Lip为特发性肺纤维化的治疗提供了参考。