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

<bold>Background:</bold> Asthma is a complex heterogeneous disease, 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. However, the peptide nature of N/OFQ limit its bioavailability and clinical efficacy. <bold>Aims:</bold> the aim of this study was to improve the bioavailability of N/OFQ by developing solid lipid nanoparticles (SLNs) loaded with a drug and characterize its effects in an animal model of asthma. <bold>Methods:</bold> 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. <bold>Results:</bold> 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. <bold>Conclusions:</bold> These results showed the positive effects of N/OFQ-SLNs on the inflammatory process and mechanical properties of the airways, suggesting that innovative nanotechnological approach, improving sustained-release properties and targeting abilities may be of therapeutic benefit for asthmatic patients.