A Biomimic Nanobullet with Ameliorative Inflammatory Microenvironment for Alzheimer's Disease Treatments.

Aß oligomers, formed prior to diagnostic marker-amyloid ß (Aß) plaques, can damage neurons and trigger neuroinflammation, which accelerate the neuronal injury in Alzheimer's disease (AD). Herein, the combination of eliminating the Aß oligomers and alleviating the inflammation is a promising therapeutic strategy for AD. However, the presence of the blood-brain barrier (BBB) and the intrinsic deficiencies of the drugs severely restrict their therapeutic effects. Inspired by the properties of rabies virus, a biomimic nanobullet (PBACR@NRs/SA) targeting neurons has been developed. The biomimic nanobullets possess the BBB penetrating character based on iron oxide nanorods; it can sequentially release rosmarinic acid and small interfering RNA targeting NF-κB triggered by microenvironment, which improve the microenvironment inflammation and realize the cure for AD. Compared with non-biomimic systems, the biomimic nanobullets exhibit a less caveolin-dependent internalization pathway, which reduces ROS production and mitochondrial fission in neurons. Therefore, the biomimic nanobullet is hopeful for the treatment of ADs and provides a promising platform for other brain diseases' treatments.

Preparation and in vitro-in vivo evaluation of novel ocular nanomicelle formulation of thymol based on glycyrrhizin.

The development of an efficient ocular drug delivery system is helpful in improving the ocular diffusion of topically delivered drugs as well as enhancing drugs therapeutic efficacy. The objective of this study was to explore the potential of self-assembled nanomicelles based on glycyrrhizin in ocular topical applications. In brief, a dipotassium glycyrrhizinate (DG)-based nanomicelle ophthalmic solution encapsulating thymol (DG-THY) was developed using a simple thin-film dispersion method. The optimal formulation featured a DG/thymol (THY) weight ratio of 9:1 and an encapsulation efficiency of 98.25 ±â€¯1.16%; the nanomicelles were ultra-small spheres with an average particle size of 3.30 ±â€¯0.39 nm, a polydispersity index of 0.22 ±â€¯0.02, and an electrically negative surface (-[10.03 ±â€¯1.31] mV) for the optimized DG-THY. This DG-THY ophthalmic solution was observed to be stable upon good storage at both 4 °C and 25 °C for 12 weeks. The DG-THY was observed to remarkably improve in vitro antioxidant activity, in vitro release, and the membrane permeation of THY. The DG-THY ophthalmic solution proved to be very well-tolerated in a rabbit model. The DG-THY ophthalmic solution also demonstrated distinct improvements in the ex vivo and in vivo intraocular permeations of THY. The DG-THY ophthalmic solution also exhibited decreased minimal inhibitory concentrations and minimum bactericidal concentrations of THY. Treatment with the DG-THY ophthalmic solution significantly relieved ocular infection symptoms in rabbit eyes by lowering the number of colony-forming units recovered from the corneas. Therefore, these results demonstrate that DG-THY may be a promising new ophthalmic formulation for the treatment of ocular diseases, especially in terms of oxidative stress-, bacteria-, and inflammation-related eye diseases.

Novel self-nanomicellizing formulation based on Rebaudioside A: A potential nanoplatform for oral delivery of naringenin.

In the study described here, we strove to develop an orally administered novel self-nanomicellizing formulation based on Rebaudioside A (RA) for delivering naringenin (NAR) with improved bioavailability and therapeutic efficacy. Our research found that RA and naringenin (NAR) could be formulated into self-assembling nanomicelles (RA-NAR) using a simple ethanol dissolution-evaporation method. We found that the RA-NAR self-assemblies comprised ultra-small micelles (5.234 ± 0.311 nm) in a uniform dispersion state (the polydispersity index was 0.243 ± 0.039) with a near-neutral surface charge (-[2.268 ± 0.729] mV). We also found that RA-NAR had a well-storage stability at 4 °C with light protection. In addition, we observed that RA-NAR exhibited enhanced apparent solubility, in-vitro permeability, and antioxidant activity. After we administered RA-NAR to rats orally, we observed an increase in area under the curve (AUC0→t) to 19,500.82 ng/mL/h versus 9324.47 ng/mL/h observed with free NAR and an increase of maximum concentration (Cmax) to 27,326.10 ng/mL from the free-NAR Cmax level of 2549.04 ng/mL. The tissue distribution assessments further demonstrated that RA-NAR could effectively increase the NAR concentration in all tested intestinal segments. Our mouse model results showed as well that oral administration of RA-NAR could efficiently protect against small intestine injuries induced by indomethacin, and the mechanisms by inhibiting proinflammatory cytokines and oxidative stress were involved in its therapeutic effect. Taken together, these findings indicate that a self-nanomicellizing formulation based on RA has great potential as a novel oral nano-drug delivery system for NAR.