Supramolecular Peptide Nanofiber/PLGA Nanocomposites for Enhancing Pulmonary Drug Delivery
Supramolecular Peptide Nanofiber/PLGA Nanocomposites for Enhancing Pulmonary Drug Delivery
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DOI：
10.1021/acsami.2c15204
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发表时间：
2022-12-07
影响因子：
9.5
通讯作者：
Nguyen，Kytai T.
中科院分区：
文献类型：
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作者：
Chintapula，Uday;Yang，Su;Nguyen，Kytai T.
有效的药物输送到肺部网站将受益于设计和合成的新的药物输送系统，可以克服各种组织和细胞的障碍。细胞穿透肽（CPP）已经显示出用于各种成像探针和治疗剂的细胞内递送的前景。尽管CPP在一定程度上提高了递送功效，但它们仍然缺乏工程范围来提高有效载荷容量并保护有效载荷免受药物递送应用中的生理环境的影响。受CPP和CPP功能化纳米颗粒的最新进展的启发，在这项工作中，我们展示了一种新型的纳米复合材料，该纳米复合材料由纤维形成的超分子CPP组成，该超分子CPP涂覆在聚乳酸-乙醇酸（PLGA）纳米颗粒上以增强肺部药物递送。这些纳米复合材料显示出纳米颗粒在各种细胞（包括原代肺上皮细胞、巨噬细胞）中的细胞内递送比裸PLGA纳米颗粒高三倍，并且在内皮细胞中增加10倍，或者比用传统单体CPP修饰的纳米颗粒增加两倍。细胞摄取研究表明，纳米复合材料可能通过混合的巨胞饮和被动能量独立机制进入细胞，随后在24小时内通过内体逃逸。纳米复合材料还显示出有效的粘液渗透。更重要的是，冻干和雾化配制的纳米复合材料粉末不影响它们的生理化学和生物活性，这进一步突出了用作肺部药物递送的稳定药物载体的转化潜力。我们期望基于肽纳米纤维的纳米复合材料，PLGA纳米颗粒可以定制设计，用于封装和提供广泛的治疗药物，包括核酸，蛋白质和小分子药物，用于可吸入系统治疗各种肺部疾病。
Effective drug delivery to pulmonary sites will benefit from the design and synthesis of novel drug delivery systems that can overcome various tissue and cellular barriers. Cell penetrating peptides (CPPs) have shown promise for intracellular delivery of various imaging probes and therapeutics. Although CPPs improve delivery efficacy to a certain extent, they still lack the scope of engineering to improve the payload capacity and protect the payload from the physiological environment in drug delivery applications. Inspired by recent advances of CPPs and CPP-functionalized nanoparticles, in this work, we demonstrate a novel nanocomposite consisting of fiber-forming supramolecular CPPs that are coated onto polylactic-glycolic acid (PLGA) nanoparticles to enhance pulmonary drug delivery. These nanocomposites show a threefold higher intracellular delivery of nanoparticles in various cells including primary lung epithelial cells, macrophages, and a 10-fold increase in endothelial cells compared to naked PLGA nanoparticles or a twofold increase compared to nanoparticles modified with traditional monomeric CPPs. Cell uptake studies suggest that nanocomposites likely enter cells through mixed macropinocytosis and passive energy-independent mechanisms, which is followed by endosomal escape within 24 h. Nanocomposites also showed potent mucus permeation. More importantly, freeze-drying and nebulizing formulated nanocomposite powder did not affect their physiochemical and biological activity, which further highlights the translative potential for use as a stable drug carrier for pulmonary drug delivery. We expect nanocomposites based on peptide nanofibers, and PLGA nanoparticles can be custom designed to encapsulate and deliver a wide range of therapeutics including nucleic acids, proteins, and small-molecule drugs when employed in inhalable systems to treat various pulmonary diseases.