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

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.

Association between Sex-Related ALOX5 Gene Polymorphisms and Lung Atopy Risk

“…Atopy is an exaggerated IgE-mediated immune response to foreign antigens that makes the immune system more sensitive to common allergic triggers [40]. It is a heterogeneous disease and can be related to other diseases [41][42][43][44][45][46][47][48]. Atopic disorders include various lung inflammatory diseases (e.g., allergic asthma and IgE-mediated components of allergic aspergillosis), allergic rhinitis, conjunctivitis, and atopic dermatitis, in which metabolic abnormalities of the leukotriene pathway play a crucial role [11][12][13][14][15][16][17][18].…”

Analgesic Peptides: From Natural Diversity to Rational Design

“…administration [215]. It is worth noting that solid lipid nanoparticles (SLN) were used to encapsulate nociceptin/orphanin FQ for reduction of airway hyperresponsiveness, which is not directly related to pain relief, although the results indicated improved bioavailability and delayedrelease [216]. Intranasal delivery was also adopted for Opiorphin administration in the form of liposomal mucoadhesive thermo-sensitive gel containing PEGylated liposomal peptide dispersion [217].…”

Overview of Antiviral Drug Therapy for COVID-19: Where Do We Stand?

“…Since the primary target of SARS-CoV-2 replication is the lung, the inhalation delivery of drugs could represent the best route of administration to cope with COVID-19. In fact, several lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD) were treated by inhaler drugs that reach a maximum pharmacological effect with minimum systemic exposure [ 105 , 106 ]. Moreover, many drugs are poorly soluble in water and/or susceptible to denaturation of the protein active ingredient [ 107 , 108 , 109 , 110 , 111 , 112 ], thus different formulations have been prepared to enhance their solubility and reduce denaturation.…”