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Peptides as surface coatings of nanoparticles that penetrate human cystic fibrosis sputum and uniformly distribute in vivo following pulmonary delivery.
Journal of Controlled Release ( IF 10.5 ) Pub Date : 2020-03-31 , DOI: 10.1016/j.jconrel.2020.03.032 Jasmim Leal 1 , Xiujuan Peng 1 , Xinquan Liu 1 , Dhivya Arasappan 2 , Dennis C Wylie 2 , Sarah H Schwartz 3 , Jason J Fullmer 3 , Bennie C McWilliams 3 , Hugh D C Smyth 1 , Debadyuti Ghosh 1
Journal of Controlled Release ( IF 10.5 ) Pub Date : 2020-03-31 , DOI: 10.1016/j.jconrel.2020.03.032 Jasmim Leal 1 , Xiujuan Peng 1 , Xinquan Liu 1 , Dhivya Arasappan 2 , Dennis C Wylie 2 , Sarah H Schwartz 3 , Jason J Fullmer 3 , Bennie C McWilliams 3 , Hugh D C Smyth 1 , Debadyuti Ghosh 1
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Therapeutic delivery of drug and gene delivery systems have to traverse multiple biological barriers to achieve efficacy. Mucosal administration, such as pulmonary delivery in cystic fibrosis (CF) disease, remains a significant challenge due to concentrated viscoelastic mucus, which prevents drugs and particles from penetrating the mucus barrier. To address this problem, we used combinatorial peptide-presenting phage libraries and next-generation sequencing (NGS) to identify hydrophilic, net-neutral charged peptide coatings that enable penetration through human CF mucus ex vivo with ~600-fold better penetration than control, improve uptake into lung epithelial cells compared to uncoated or PEGylated-nanoparticles, and exhibit enhanced uniform distribution and retention in the mouse lung airways. These peptide coatings address multiple delivery barriers and effectively serve as excellent alternatives to standard PEG surface chemistries to achieve mucus penetration and address some of the challenges encountered using these chemistries. This biomolecule-based strategy can address multiple delivery barriers and hold promise to advance efficacy of therapeutics for diseases like CF.
中文翻译：
肽作为纳米颗粒的表面涂层，可穿透人囊性纤维化痰并在肺部递送后在体内均匀分布。
药物的治疗性递送和基因递送系统必须穿越多个生物学障碍才能达到功效。粘膜给药，例如在囊性纤维化（CF）疾病中的肺部递送，由于粘弹性浓的粘液而阻止药物和颗粒穿透粘液屏障，仍然是一项重大挑战。为了解决这个问题，我们使用了组合肽呈递噬菌体文库和下一代测序（NGS）来鉴定亲水的，净中性电荷的肽涂层，该涂层能够通过人CF粘液进行离体穿透，其穿透力比对照高约600倍，与未包被或聚乙二醇化的纳米颗粒相比，可改善对肺上皮细胞的摄取，并在小鼠肺气道中显示出增强的均匀分布和保留。这些肽涂层解决了多个传递障碍，并有效地替代了标准PEG表面化学方法，以实现粘液渗透并解决了使用这些化学方法时遇到的一些挑战。这种基于生物分子的策略可以解决多个传递障碍，并有望提高治疗剂对CF等疾病的疗效。
更新日期：2020-04-01
中文翻译：
肽作为纳米颗粒的表面涂层，可穿透人囊性纤维化痰并在肺部递送后在体内均匀分布。
药物的治疗性递送和基因递送系统必须穿越多个生物学障碍才能达到功效。粘膜给药，例如在囊性纤维化（CF）疾病中的肺部递送，由于粘弹性浓的粘液而阻止药物和颗粒穿透粘液屏障，仍然是一项重大挑战。为了解决这个问题，我们使用了组合肽呈递噬菌体文库和下一代测序（NGS）来鉴定亲水的，净中性电荷的肽涂层，该涂层能够通过人CF粘液进行离体穿透，其穿透力比对照高约600倍，与未包被或聚乙二醇化的纳米颗粒相比，可改善对肺上皮细胞的摄取，并在小鼠肺气道中显示出增强的均匀分布和保留。这些肽涂层解决了多个传递障碍，并有效地替代了标准PEG表面化学方法，以实现粘液渗透并解决了使用这些化学方法时遇到的一些挑战。这种基于生物分子的策略可以解决多个传递障碍，并有望提高治疗剂对CF等疾病的疗效。
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