Peptides hold promise as therapeutics, as they have high bioactivity and specificity, good aqueous solubility, and low toxicity. However, they typically suffer from short circulation half-lives in the body. To address this issue, here, we have developed a method for encapsulation of an innate-immune targeted hexapeptide into nanoparticles using safe non-toxic FDA-approved materials. Peptide-loaded nanoparticles were formulated using a two-stage microfluidic chip. Microfluidic-related factors (i.e., flow rate, organic solvent, theoretical drug loading, PLGA type, and concentration) that may potentially influence the nanoparticle properties were systematically investigated using dynamic light scattering and transmission electron microscopy. The pharmacokinetic (PK) profile and biodistribution of the optimised nanoparticles were assessed in mice. Peptide-loaded lipid shell-PLGA core nanoparticles with designated size (~400 nm) and a sustained in vitro release profile were further characterized in vivo. In the form of nanoparticles, the elimination half-life of the encapsulated peptide was extended significantly compared with the peptide alone and resulted in a much higher distribution into the lung. These novel nanoparticles with lipid shells have considerable potential for increasing the circulation half-life and improving the biodistribution of therapeutic peptides to improve their clinical utility, including peptides aimed at treating lung-related diseases.

中文翻译：

---

用于输送小肽的微流体方法的优化


肽作为治疗药物具有前景，因为它们具有高生物活性和特异性、良好的水溶性和低毒性。然而，它们在体内的循环半衰期通常较短。为了解决这个问题，我们在这里开发了一种使用 FDA 批准的安全无毒材料将先天免疫靶向六肽封装到纳米颗粒中的方法。使用两级微流控芯片配制负载肽的纳米颗粒。使用动态光散射和透射电子显微镜系统地研究了可能影响纳米颗粒特性的微流体相关因素（即流速、有机溶剂、理论载药量、PLGA 类型和浓度）。在小鼠中评估了优化纳米颗粒的药代动力学 (PK) 特征和生物分布。具有指定尺寸（约 400 nm）和体外持续释放特性的肽负载脂质壳-PLGA 核心纳米颗粒在体内得到了进一步表征。与单独的肽相比，纳米颗粒形式的封装肽的消除半衰期显着延长，并导致更高的肺部分布。这些具有脂质壳的新型纳米颗粒在延长循环半衰期和改善治疗性肽的生物分布以提高其临床效用（包括旨在治疗肺部相关疾病的肽）方面具有巨大的潜力。