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载有孤啡肽/痛敏肽（N/OFQ）的固体脂质纳米粒的制备及其在气道高反应性小鼠模型中的表征

Formulation of Solid Lipid Nanoparticles Loaded with Nociceptin/Orphanin FQ (N/OFQ) and Characterization in a Murine Model of Airway Hyperresponsiveness.

作者信息

Mirra Davida, Spaziano Giuseppe, Esposito Renata, Santonocito Debora, Filosa Rosanna, Roviezzo Fiorentina, Malgieri Gaetano, D'Abrosca Gianluca, Iovino Pasquale, Gallelli Luca, Fattorusso Roberto, Puglia Carmelo, D'Agostino Bruno

机构信息

Department of Environmental Biological and Pharmaceutical Sciences and Technologies, University of Campania "Luigi Vanvitelli", 81100 Caserta, Italy.

Department of Drug and Health Sciences, University of Catania, 95125 Catania, Italy.

出版信息

Pharmaceuticals (Basel). 2022 Sep 29;15(10):1210. doi: 10.3390/ph15101210.

DOI:10.3390/ph15101210
PMID:36297323
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9609590/
Abstract

Asthma is characterized by chronic inflammation and a variable degree of airway hyperresponsiveness (AHR). Our previous papers documented a role for Nociceptin/Orphanin FQ (N/OFQ) and its receptor N/OFQ peptide (NOP) in AHR. Therefore, the aim of this study was to improve the bioavailability of N/OFQ by developing solid lipid nanoparticles (SLNs). N/OFQ-loaded SLNs were prepared by the Quasi Emulsion Solvent Diffusion (QESD) technique and then characterized. Brown Norway rats were sensitized to ovalbumin (OVA) and treated with an intratracheal administration of saline solution or N/OFQ-SLN. Then, 24 h after the last challenge, functional histological and molecular evaluations were performed. SLNs showed a mean diameter of 233 ± 0.03 nm, a polydispersity index (PDI) value around 0.28 ± 0.02 and a drug release percentage of 84.3. The in vitro release of N/OFQ from SLNs showed that the release of the peptide starts already after two hours of incubation. Animals receiving N/OFQ-SLN showed a significative decrease in allergen-induced AHR compared to the control group. These results showed the positive effects of N/OFQ-SLNs on the inflammatory process and on the mechanical properties of the airways, suggesting that the innovative nanotechnological approach may be therapeutically beneficial for asthmatic patients.

摘要

哮喘的特征是慢性炎症和不同程度的气道高反应性（AHR）。我们之前的论文记录了痛敏肽/孤啡肽FQ（N/OFQ）及其受体N/OFQ肽（NOP）在气道高反应性中的作用。因此，本研究的目的是通过开发固体脂质纳米粒（SLN）来提高N/OFQ的生物利用度。采用准乳液溶剂扩散（QESD）技术制备了负载N/OFQ的SLN，然后对其进行表征。用卵清蛋白（OVA）致敏棕色挪威大鼠，并通过气管内给予盐溶液或N/OFQ-SLN进行治疗。然后，在最后一次激发后24小时，进行功能、组织学和分子评估。SLN的平均直径为233±0.03nm，多分散指数（PDI）值约为0.28±0.02，药物释放率为84.3%。N/OFQ从SLN的体外释放表明，在孵育两小时后肽就开始释放。与对照组相比，接受N/OFQ-SLN的动物在过敏原诱导的气道高反应性方面有显著降低。这些结果表明N/OFQ-SLN对炎症过程和气道力学性能有积极影响，表明这种创新的纳米技术方法可能对哮喘患者有治疗益处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d88c/9609590/2a7b464eb995/pharmaceuticals-15-01210-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d88c/9609590/ffc346c35667/pharmaceuticals-15-01210-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d88c/9609590/e416913cf173/pharmaceuticals-15-01210-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d88c/9609590/984ec9395881/pharmaceuticals-15-01210-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d88c/9609590/a594e98e8e5f/pharmaceuticals-15-01210-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d88c/9609590/5c001750c21c/pharmaceuticals-15-01210-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d88c/9609590/b0045f6be864/pharmaceuticals-15-01210-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d88c/9609590/0c275b2abfbc/pharmaceuticals-15-01210-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d88c/9609590/2a7b464eb995/pharmaceuticals-15-01210-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d88c/9609590/ffc346c35667/pharmaceuticals-15-01210-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d88c/9609590/e416913cf173/pharmaceuticals-15-01210-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d88c/9609590/984ec9395881/pharmaceuticals-15-01210-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d88c/9609590/a594e98e8e5f/pharmaceuticals-15-01210-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d88c/9609590/5c001750c21c/pharmaceuticals-15-01210-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d88c/9609590/b0045f6be864/pharmaceuticals-15-01210-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d88c/9609590/0c275b2abfbc/pharmaceuticals-15-01210-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d88c/9609590/2a7b464eb995/pharmaceuticals-15-01210-g008.jpg

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