Abstract
To prepare a binary formulation delivering miRNA-146 and evaluate a nucleic acid nasal delivery system by investigating its pharmacodynamic effects in allergic rhinitis. The gel/NPs/miR-146a thermosensitive in situ chitosan hydrogel carrying a nucleic acid was prepared and evaluated for its characteristics, including temperature sensitivity, gel strength, mucosal adhesion and drug release profile. After nasal administration of the formulation to ovalbumin-sensitized rats, the treatment of allergic rhinitis was verified by assessing nasal symptoms, hematology, hematoxylin-eosin (HE) staining and immunohistochemistry. Western Blot(WB) was used to analyze nasal inflammatory factors as well as miRNA-146-related factors, and the miR146 expression level was measured by PCR. Subsequently, the effects of the gel/NPs/miR-146a binary formulation were evaluated for the nasal delivery of nucleic acids in rhinitis therapy. The prepared binary formulation quickly formed a gel in the nasal cavity at a temperature of 34 °C with good mucosal adhesion, which delivered nucleic acids into the nasal mucosa stably and continuously. Gel/NPs/miR-146a was able to sustain the delivery of miRNA into the mucosa after nasal administration. When compared with the monolithic formulations, the gel/NPs/miR-146a binary formulation performed better regarding its nucleic acid delivery ability and pharmacodynamic effects. The gel/NPs/miR-146a binary preparation has a suitable nasal mucosal drug delivery ability and has a positive pharmacodynamic effect for the treatment of ovalbumin-induced rhinitis in rats. It can serve as a potential nucleic acid delivery platform for the treatment of allergic rhinitis.
Highlights
Allergic rhinitis (AR) is a type I allergic inflammatory disease that is of the nasal mucosa induced by Immunoglobulin E (IgE) under the chemotaxis of a variety of inflammatory cytokines after a specific individual comes in contact with antigens
Nanoparticles are currently widely used in drug and gene delivery platforms
Nanoparticle delivery platforms are increasingly combined with other biological materials to form a hybrid system with novel application prospects [33]
Summary
Allergic rhinitis (AR) is a type I allergic inflammatory disease that is of the nasal mucosa induced by Immunoglobulin E (IgE) under the chemotaxis of a variety of inflammatory cytokines after a specific individual comes in contact with antigens. Naked miRNA has difficulty penetrating the extracellular barrier and is degraded in vivo It often has a short retention time because of removal by the nasal cilia, reducing the contact time of the drug with nasal epithelial cells [12]. To remove the limitation of applying miRNA in the nasal mucosa, we sought to design a safe and stable formulation to deliver miR-146afor the local treatment of allergic rhinitis. The rationally designed miRNA-NPs/CP thermosensitive hydrogel binary formulation provides the potential for realizing nucleic acid drug therapy for nasal diseases. Using a microplate reader (λex/em = 550/570 nm), (Infinite F200Pro, TECAN, Männedorf, Switzerland), the miRNA in the supernatant was quantified according to the calibration curve of miR-146a, and all experiments were repeated three times. The loading efficiency of miRNA was calculated as follows [26]:
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
