Nanotechnology for enhanced nose-to-brain drug delivery in treating neurological diseases.

Despite the increasing global incidence of brain disorders, achieving sufficient delivery towards the central nervous system (CNS) remains a formidable challenge in terms of translating into improved clinical outcomes. The brain is highly safeguarded by physiological barriers, primarily the blood-brain barrier (BBB), which routinely excludes most therapeutics from entering the brain following systemic administration. Among various strategies investigated to circumvent this challenge, intranasal administration, a noninvasive method that bypasses the BBB to allow direct access of drugs to the CNS, has been showing promising results. Nanotechnology-based drug delivery systems, in particular, have demonstrated remarkable capacities in overcoming the challenges posed by nose-to-brain drug delivery and facilitating targeted drug accumulation within the brain while minimizing side effects of systemic distribution. This review comprehensively summarizes the barriers of nose-to-brain drug delivery, aiming to enhance our understanding of potential physiological obstacles and improve the efficacy of nasal delivery in future trials. We then highlight cutting-edge nanotechnology-based studies that enhance nose-to-brain drug delivery in three key aspects, demonstrating substantial potential for improved treatment of brain diseases. Furthermore, the attention towards clinical studies will ease the regulatory approval process for nasal administration of nanomedicines targeting brain disease.

Cross-Coupling of Cyclobutenone N-Tosylhydrazones with Organohalides: Access to Conjugated Enynes and Enallenes via a Strained Allylpalladium Intermediate.

A palladium-catalyzed cross-coupling reaction of cyclobutenone N-tosylhadrazones with organohalides is disclosed. The protocol involves the generation of a strained allylpalladium intermediate from readily available starting materials through palladium carbene migratory insertion, which undergoes electrocyclic ring opening and ß-hydride elimination for the production of conjugated enynes and enallenes. The broad substrate scope, good to excellent yields, and tunable product diversity make the protocol potentially useful in organic synthesis.

Palladium-Catalyzed Carbene Coupling Reactions of Cyclobutanone N-Sulfonylhydrazones.

Described herein are the palladium-catalyzed cross-coupling reactions of cyclobutanone-derived N-sulfonylhydrazones with aryl or benzyl halides, suggesting that the metal carbene process and ß-hydride elimination can smoothly occur in strained ring systems. Structurally diversified products including cyclobutenes, methylenecyclobutanes, and conjugated dienes are selectively afforded in good to excellent yields. Preliminary success in asymmetric carbene coupling reactions in strained ring systems has been achieved, providing a promising route for the synthesis of enantioenriched four-membered-ring molecules.