Chitosan Hydrogel Doped with PEG-PLA Nanoparticles for the Local Delivery of miRNA-146a to Treat Allergic Rhinitis

• Published in: Pharmaceutics Vol. 12; no. 10; p. 907
• Main Authors: Su, Yu, Sun, Bixi, Gao, Xiaoshu, Liu, Shuwen, Hao, Rubin, Han, Bing
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 23.09.2020; MDPI
• Subjects: Acids; Allergens; allergic rhinitis; Allergies; Antigens; binary formulation; Biotechnology; Cytokines; Gene expression; Hydrogels; Immune system; Inflammation; MicroRNAs; miR-146a; Nanoparticles; Nose; Particle size; Permeability; Polyethylene glycol; Retention; Rhinitis; China
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics12100907

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.