A new approach to developing diagnostics and therapeutics: Aggregation-induced emission-based fluorescence turn-on.

Fluorescence imaging is a promising visualization tool and possesses the advantages of in situ response and facile operation; thus, it is widely exploited for bioassays. However, traditional fluorophores suffer from concentration limits because they are always quenched when they aggregate, which impedes applications, especially for trace analysis and real-time monitoring. Recently, novel molecules with aggregation-induced emission (AIE) characteristics were developed to solve the problems encountered when using traditional organic dyes, because these new molecules exhibit weak or even no fluorescence when they are in free movement states but emit intensely upon the restriction of intramolecular motions. Inspired by the excellent performances of AIE molecules, a substantial number of AIE-based probes have been designed, synthesized, and applied to various fields to fulfill diverse detection tasks. According to numerous experiments, AIE probes are more practical than traditional fluorescent probes, especially when used in bioassays. To bridge bioimaging and materials engineering, this review provides a comprehensive understanding of the development of AIE bioprobes. It begins with a summary of mechanisms of the AIE phenomenon. Then, the strategies to realize accurate detection using AIE probes are discussed. In addition, typical examples of AIE-active materials applied in diagnosis, treatment, and nanocarrier tracking are presented. In addition, some challenges are put forward to inspire more ideas in the promising field of AIE-active materials.

Effectiveness of idebenone nanorod formulations in the treatment of Alzheimer's disease.

Idebenone (IDB) has demonstrated the potential to treat mitochondrial and neurodegenerative diseases, including Alzheimer's disease (AD). However, its therapeutic effects are compromised by poor compliance due to low bioavailability. The objective of this study is to fabricate IDB nanorods (IDBNRs) to improve oral bioavailability and increase concentrations in the brain in order to enhance therapeutic effects of IDB in the treatment of AD. IDBNRs showed desired sizes and rod-shaped morphologies. The release rate and the antioxidant activity of IDBNRs were improved relative to other delivery routes. The plasma and brain concentrations were enhanced due to rapid release into the systemic circulation. In behavioral tests, mice treated orally with IDBNRs showed amelioration of AD-induced impairment of learning and memory. Thus, because of improved efficiency of drug delivery, doses can be reduced, and the compliance and therapeutic experience of patients can be improved. IDBNRs may provide effective and convenient treatments for AD patients in the future.

A carbohydrate polymer is a critical variable in the formulation of drug nanocrystals: a case study of idebenone.

Objective: Stabilizers, especially carbohydrate polymers, have been shown to be necessary for the stabilization of drug nanocrystals. However, the impacts of select stabilizers on the in vitro and in vivo efficacy of therapeutics have rarely been reported. The aim of this study was to evaluate the importance of stabilizers in the formulation of drug nanocrystals.Research design and methods: Idebenone nanocrystals (IDBNC) stabilized by various stabilizers were formulated using a milling method. The in vitro dissolution profiles in water and in situ absoprtion were compared. Finally, an in vivo pharmacokinetic study was performed.Results: The IDBNC profiles were found to have acceptable sizes and similar morphology and crystallinity. The dissolution profiles of IDBNC stabilized by different stabilizers were notably different, indicating the critical influence of stabilizers on the release rate of IDB. The Soluplus-stabilized IDBNC (IDBNC400 nm/Soluplus) achieved better absorption than HPMC stabilized IDBNC (IDBNC400 nm/HPMC). The pharmacokinetic study demonstrated that Soluplus-stabilized IDBNC had preferable kinetics, with an AUC0-24h of IDBNC400 nm/Soluplus (3.08-fold relative to IDB suspension), compared to IDBNC400 nm/HPMC (1.88-fold).Conclusions: Choice of stabilizer plays an important role in the formulation of IDBNC. We anticipate that the role of stabilizers in the pharmacokinetic disposition of IDBNC has significant implications for a wide range of other drug crystal formulations.

Impacts of particle shapes on the oral delivery of drug nanocrystals: Mucus permeation, transepithelial transport and bioavailability.

For drug nanocrystals (NCs), particle shapes can affect aqueous solubility, dissolution rate and oral bioavailability. However, the effects of particle shapes on the transport of NCs across the intestinal barriers remain unclear. In the present study, spherical, rod-shaped and flaky NCs (SNCs, RNCs, and FNCs) were prepared and characterized. Meanwhile, fluorescence resonance energy transfer molecules were used to track the fate of intact NCs. Results showed that particle shapes had great influences on the mucus permeation, cellular uptake and transmembrane transport of NCs, and RNCs exhibited the best absorption efficiency. Besides, we found that endoplasmic reticulum/Golgi and Golgi/plasma membrane pathways might be involved in the transcytosis and exocytosis of NCs. Moreover, the oral bioavailability study showed that AUC0-24h of RNCs was 1.44-fold and 1.8-fold higher than that of SNCs and FNCs, respectively. Collectively, these results provided compelling evidences that RNCs could potentially improve the absoption efficacy of NCs in oral delivery. Our findings give deep insights into the impacts of particle shapes on the oral absoption of NCs and provide valuable knowledge for rational design of optimized NCs for oral drug delivery.