Nanocapsule-Based Reactive Nano-Fragrances with Slow-Release and Antibacterial Performances for Applications of Commodities.

Fragrances are widely used in everyday life. However, too fast volatilization rates and poor adhesion on substrates limit their applications. In this study, reactive nano-fragrance based on cyanuric chloride (CYC)-modified chitosan (CSCYC) were prepared by a solvent evaporation method. First, CS-CYC was synthesized. Subsequently, CS and CS-CYC were utilized to prepare nano-fragrances. The results demonstrated that adding CS and CS-CYC could significantly improve the fragrance encapsulation efficiency and reduce the release rate of phenylethanol. phenylethanol Moreover, the adhesion of nano-capsules on commodities was improved with CS by forming hydrogen bonds. CYC on the surface of the nanocapsules further enhanced the conglutination of nano-fragrances on commodities by a condensation reaction with wallpaper. Additionally, the addition of both CS and CS-CYC imparted antibacterial activity for the nano-fragrances against Gram-positive and Gram-negative bacteria with excellent biosafety. Therefore, the reactive nano-fragrances with antimicrobial activity and slow-release properties could provide a comfortable and healthy living environment, making them have vast application potential.

Self-Catalytic Small Interfering RNA Nanocarriers for Synergistic Treatment of Neurodegenerative Diseases.

Gene therapy has shown great potential for neurodegenerative diseases with complex pathology. However, its therapeutic effect is limited due to the delivery barriers and its own single function. Herein, self-catalytic small interfering RNA (siRNA) nanocarriers (S/Ce-PABMS) are developed to catalyze delivery process and treatment process for synergistic treatment of neurodegenerative diseases. On the one hand, the rough surface of the S/Ce-PABMS mediated by ceria (CeO2 ) nanozymes can catalyze cellular uptake in the delivery process, so that S/Ce-PABMS with acetylcholine analogs penetrate the blood-brain barrier and enter neurons more effectively. On the other hand, the CeO2 nanozymes can catalyze the treatment process by scavenging excess reactive oxygen species, and cooperate with siRNA-targeting SNCA to decrease the α-synuclein (α-syn) aggregation and alleviate the Parkinsonian pathology. Moreover, the S/Ce-PABMS treatment reduces the number of activated microglia and regulates the release of inflammatory cytokine, thereby relieving neuroinflammation. After treatment with S/Ce-PABMS, dyskinesia in Parkinson's disease model mice is significantly alleviated. The finding shows that the self-catalytic nanocarriers, S/Ce-PABMS, have great potential in the treatment of neurodegenerative diseases.

Intranasal Administration of Self-Oriented Nanocarriers Based on Therapeutic Exosomes for Synergistic Treatment of Parkinson's Disease.

The treatment of Parkinson's disease (PD) has been hindered by the complex pathologies and multiple membrane barriers during drug delivery. Although exosomes derived from mesenchymal stem cells (MSCs) have great potential for PD, MSC-derived exosomes alone could not fully meet the therapeutic requirements due to their limitation in therapy and delivery. Here, we develop a self-oriented nanocarrier called PR-EXO/PP@Cur that combines therapeutic MSC-derived exosomes with curcumin. PR-EXO/PP@Cur can be self-oriented across the multiple membrane barriers and directly release drugs into the cytoplasm of target cells after intranasal administration. With enhanced accumulation of drugs in the action site, PR-EXO/PP@Cur achieves three-pronged synergistic treatment to deal with the complex pathologies of PD by reducing α-synuclein aggregates, promoting neuron function recovery, and alleviating the neuroinflammation. After treatment with PR-EXO/PP@Cur, the movement and coordination ability of PD model mice are significantly improved. These results show that PR-EXO/PP@Cur has great prospects in treatment of PD or other neurodegenerative diseases.

Osthole-Loaded Nanoemulsion Enhances Brain Target in the Treatment of Alzheimer's Disease via Intranasal Administration.

Osthole (OST) is a natural coumarin compound that exerts multiple pharmacologic effects. However, the poor water solubility and the low oral absorption of OST limit its clinical application for the treatment of neurologic diseases. A suitable preparation needs to be tailored to evade these unfavourable properties of OST. In this study, an OST nanoemulsion (OST-NE) was fabricated according to the pseudoternary phase diagram method, which was generally used to optimize the prescription in light of the solubility of OST in surfactants and cosurfactants. The final composition of OST-NE was 3.6% of ethyl oleate as oil phase, 11.4% of the surfactant (polyethylene glycol ester of 15-hydroxystearic acid: polyoxyethylene 35 castor oil = 1 : 1), 3% of polyethylene glycol 400 as cosurfactant, and 82% of the aqueous phase. The pharmacokinetic study of OST-NE showed that the brain-targeting coefficient of OST was larger by the nasal route than that by the intravenous route. Moreover, OST-NE inhibited cell death, decreased the apoptosis-related proteins (Bax and caspase-3), and enhanced the activity of antioxidant enzymes (superoxide dismutase and glutathione) in L-glutamate-induced SH-SY5Y cells. OST-NE improved the spatial memory ability, increased the acetylcholine content in the cerebral cortex, and decreased the activity of acetylcholinesterase in the hippocampus of Alzheimer's disease model mice. In conclusion, this study indicates that the bioavailability of OST was improved by using the OST-NE via the nasal route. A low dose of OST-NE maintained the neuroprotective effects of OST, such as inhibiting apoptosis and oxidative stress and regulating the cholinergic system. Therefore, OST-NE can be used as a possible alternative to improve its bioavailability in the prevention and treatment of Alzheimer's disease.

Nano-Aromatic Drugs Based on Mesoporous Silica Nanoparticles and Bergamot Essential Oil for Anti-Depression.

Depression is a mental disorder characterized by low mood as the main pathological feature. Current medications for depression have long treatment cycles and serious side effects. Aromatherapy can alleviate depression in a "moistening things silently" way, but the fast evaporation rate of aromatic drugs weakens the effect of aromatherapy. In this study, we designed and prepared nano-aromatic drugs with slow release for anti-depressant application. We first synthesized rod-shaped mesoporous silica nanoparticles (MSNs) and encapsulated bergamot essential oil. These nanoaromatic drugs were named BEO@MSNs. Subsequently, we analyzed the pore properties of MSNs and BEO@MSNs. Further, we explored the thermal stability, encapsulation efficiency, and slow-release properties of bergamot essential oil in BEO@MSNs. Finally, we used BEO@MSNs to alleviate depression in mice while constructing depression model mice via corticosterone. The results showed that BEO@MSNs had excellent anti-depressant effects and biosafety.

Traceable Nano-Biohybrid Complexes by One-Step Synthesis as CRISPR-Chem Vectors for Neurodegenerative Diseases Synergistic Treatment.

Abnormal protein aggregations are essential pathological features of neurodegenerative diseases. Eliminating while inhibiting the regeneration of these protein aggregates is considered an effective treatment strategy. Herein, the CRISPR/Cas9 gene-editing tool is employed to inhibit the regeneration of disease-related proteins, while chemical drugs are applied to eliminate the proteins that are produced. To efficiently deliver CRISPR-chem drugs into brain lesions, traceable nano-biohybrid complexes (F-TBIO) are constructed by one-step synthesis and CRISPR/Cas9 plasmids (CF-TBIO) are loaded in a controllable manner. CF-TBIO can knock out the BACE1 gene and reduce the burden of amyloid-ß, and thereby significantly improve the cognitive abilities of 2xTg-AD mice. In particular, by prolonging the dosing interval, the pathological damage and behavioral abilities of 2xTg-AD mice are still significantly improved. During the therapeutic process, CF-TBIO with a high relaxation rate provides accurate imaging signals in the complex brain physiological environment. The finding shows that CF-TBIO has great potential to serve as a CRISPR-chem drug-delivery platform for neurodegenerative diseases therapy.