Effective treatments for neurodegenerative diseases need to be developed. MiR132 is abundantly expressed in the brain, and it modulates neuron morphology and plays a key role in maintaining neuron survival. Regulating miR132 can effectively improve the symptoms of Alzheimer's disease. It can also reduce cell death after cerebral hemorrhage, improve the microenvironment of hematoma lesions and provide a certain protective effect from brain damage after cerebral ischemia. MiR132 has great potential in the treatment of cerebral ischemia and Alzheimer's disease. To prevent the decline of miR132 of miR132 levels in the blood, we used mouse and rat models of Alzheimer's disease with ischemic brain injury, and then delivered Wheat germ agglutinin (WGA)-NPs-miR132 intranasally to treat neurological damage after cerebral ischemia. Synaptic protein expression levels in Alzheimer's mouse models increased significantly after administration. We propose that, nasal delivery of WGA-NPs-miR132 is an interesting novel therapeutic approach for the treatment of neurodegenerative diseases.

Effective nose-to-brain delivery needs to be developed to treat neurodegenerative diseases. Regulating miR-124 can effectively improve the symptoms of ischemic brain injury and provide a certain protective effect from brain damage after cerebral ischemia. We used rat models of middle cerebral artery occlusion (t-MCAO) with ischemic brain injury, and we delivered RVG29-NPs-miR124 intranasally to treat neurological damage after cerebral ischemia. Rhoa and neurological scores in rats treated by intranasal administration of RVG29-PEG-PLGA/miRNA-124 were significantly lower than those in PEG-PLGA/miRNA-124 nasal administration and RVG29-PLGA/miRNA-124 nasal administration group treated rats. These results indicate that the nose-to-brain delivery of PLGA/miRNA-124 conjugated with PEG and RVG29 alleviated the symptoms of cerebral ischemia-reperfusion injury. Thus, nasal delivery of RVG29-PEG-PLGA/miRNA-124 could be a new method for treating neurodegenerative diseases.

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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.

Studies have shown that microRNA-133 (miR-133) plays a positive role in the growth of cardiac myocytes, the maintenance of cardiac homeostasis, and the recovery of cardiac function, which is of great significance for the recovery of acute myocardial infarction. However, the delivery of miRNA to the site of action remains a challenge at present. The purpose of this study was to design an ideal carrier to facilitate the delivery of miR-133 to the infarct lesion for cardiac protection. A disease model was constructed by ligating the left anterior descending coronary artery of rats, and polyethylene glycol (PEG)-polylactic acid (PLA) nanoparticles modified with arginine-glycine-aspartic acid tripeptide (RGD) carrying miR-133 were injected via the tail vein. The effects of miR-133 were evaluated from multiple perspectives, including cardiac function, blood indexes, histopathology, and myocardial cell apoptosis. The results showed that RGD-PEG-PLA maintained a high level of distribution in the hearts of model rats, indicating the role of the carrier in targeting the heart infarction lesions. RGD-PEG-PLA/miR-133 alleviated cardiac histopathological changes, reduced the apoptosis of cardiomyocytes, and reduced the levels of factors associated with myocardial injury. Studies on the mechanism of miR-133 by immunohistochemistry and polymerase chain reaction demonstrated that the expression level of Sirtuin3 (SIRT3) was increased and that the expression of adenosine monophosphate activated protein kinase (AMPK) decreased in myocardial tissue. In summary, the delivery of miR-133 by RGD-PEG-PLA carrier can achieve cardiac lesion accumulation, thereby improving the cardiac function damage and reducing the myocardial infarction area. The inhibition of cardiomyocyte apoptosis, inflammation, and oxidative stress plays a protective role in the heart. The mechanism may be related to the regulation of the SIRT3/AMPK pathway.

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