The unique anatomical and physiological connections between the nasal cavity and brain provide a pathway for bypassing the blood–brain barrier to allow for direct brain-targeted drug delivery through nasal administration. There are several advantages of nasal administration compared with other routes; for example, the first-pass effect that leads to the metabolism of orally administered drugs can be bypassed, and the poor compliance associated with injections can be minimized. Nasal administration can also help maximize brain-targeted drug delivery, allowing for high pharmacological activity at lower drug dosages, thereby minimizing the likelihood of adverse effects and providing a highly promising drug delivery pathway for the treatment of central nervous system diseases. The aim of this review article was to briefly describe the physiological structures of the nasal cavity and brain, the pathways through which drugs can enter the brain through the nose, the factors affecting brain-targeted nasal drug delivery, methods to improve brain-targeted nasal drug delivery systems through the application of related biomaterials, common experimental methods used in intranasal drug delivery research, and the current limitations of such approaches, providing a solid foundation for further in-depth research on intranasal brain-targeted drug delivery systems (see Graphical Abstract).

Solanum nigrum Linn., is a common edible medicinal herb of the Solanaceae family which is native to Southeast Asia and is now widely distributed in temperate to tropical regions of Europe, Asia, and America. Traditionally, it has been used to treat various cancers, acute nephritis, urethritis, leucorrhea, sore throat, toothache, dermatitis, eczema, carbuncles, and furuncles. Up to now, 188 chemical constituents have been identified from S. nigrum. Among them, steroidal saponins, alkaloids, phenols, and polysaccharides are the major bioactive constituents. Investigations of pharmacological activities of S. nigrum revealed that this edible medicinal herb exhibits a wide range of therapeutic potential, including antitumor, anti-inflammatory, antioxidant, antibacterial, and neuroprotective activities both in vivo and in vitro. This article presents a comprehensive and systematic overview of the botanical, traditional uses, phytochemical compositions, pharmacological properties, clinical trials, and toxicity of S. nigrum to provide the latest information for further exploitation and applications of S. nigrum in functional foods and medicines.

Objective: Postoperative delirium is common after general anesthesia in older patients. However, there are currently no effective preventive measures. This study investigated the effect of repeated intranasal administration of different insulin doses before surgery on postoperative delirium in older patients with esophageal cancer, and the possible mechanism for its efficacy. Methods: In this randomized, placebo-controlled, double-blind, parallel-group study, 90 older patients were randomly assigned to either a Control (normal saline), Insulin 1 (20 U/0.5 mL intranasal insulin), or Insulin 2 (30 U/0.75 mL intranasal insulin) group. Delirium was assessed on postoperative days 1 (T2), 2 (T3), and 3 (T4) using the Confusion Assessment Method for the Intensive Care Unit. Serum τ and Aβ protein levels were measured at T0 (before insulin/saline administration), T1 (end of surgery), T2, T3 and T4. Results: The Insulin 2 group had a significantly lower prevalence of delirium compared to the Control and Insulin 1 groups three days after surgery. Compared to baseline, τ and Aβ protein levels increased significantly at T1–T4. Compared to the Control group, the Insulin 1 and 2 groups had significantly lower τ and Aβ protein levels at T1–T4, and the Insulin 2 group had significantly lower levels than the Insulin 1 group at T1–T2. Conclusion: The administration of 30 U of intranasal insulin twice daily, from 2 days preoperatively until 10 minutes preanesthesia on the day of surgery, can significantly reduce postoperative delirium in older patients undergoing radical esophagectomy. It can also decrease postoperative τ and Aβ protein expression without causing hypoglycemia. Clinical Trial Registration: This study was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn, with the unique identifier: ChiCTR2100054245; December 11, 2021).

Background: Postoperative delirium (POD) is a common neurological complication associated with valve replacement. Preoperative sleep disturbance is a risk factor for POD development, and nasal insulin modulates the sleep-wake cycle. This study investigated the beneficial effects of intranasal insulin pretreatment on preoperative sleep quality and reducing POD in patients undergoing valve replacement for rheumatic heart disease. Patients and Methods: This prospective, single-center, randomized controlled trial (RCT) included 76 adult patients aged 18– 65 years undergoing valve surgery with cardiopulmonary bypass who were randomly allocated to receive intranasal insulin or normal saline interventions two days before surgery. POD incidence was on postoperative days 1 (T3), 2 (T4), and 3 (T5). Before the first intervention (T0), 1 d before surgery (T1), and before anesthesia on the day of surgery (T2), sleep quality was assessed and serum cortisol concentrations were measured. At T1 and T2, sleep quality related indicators monitored by sleep monitoring watches from the previous night were recorded. Results: Compared with the normal saline group, 3 days after surgery, the insulin group showed a significantly reduced incidence of POD; significantly increased deep sleep, REM sleep, deep sleep continuity, and total sleep quality scores at T1 and T2; and significantly reduced serum cortisol concentration, PSQI scale, light sleep ratio, and wakefulness at T1 and T2. Conclusion: The administration of 20 U of intranasal insulin twice daily, from 2 days preoperatively until 10 minutes preanesthesia on the day of surgery, can improved preoperative sleep quality significantly and reduced POD incidence in patients with rheumatic heart disease undergoing valve replacement. Clinical Trial Registration: This study was registered with the Chinese Clinical Trial Registry (www.chictr.org.cn, with the unique identifier ChiCTR2100048515; July 9, 2021).

Isodon rubescens is a medicinal and food plant, often eaten as a wild vegetable in ancient China, and has been widely used for decades to treat sore throats, tonsillitis, colds and headaches, bronchitis, chronic hepatitis, joint rheumatism, snake and insect bites, and various cancers. This comprehensive and systematic review of the ethnomedicinal uses, phytochemical composition, pharmacological activity, quality control and toxicology of I. rubescens provides updated information for the further development and application in the fields of functional foods and new drugs research. To date, a total of 324 substances have been isolated and identified from the plant, including terpenoids, flavonoids, polyphenols, alkaloids, amino acids, and volatile oils. Among these substances, diterpenoids are the most important and abundant bioactive components. In the past decades pharmacological studies have shown that I. rubescens has significant biological activities, especially in the modulation of antitumor and multidrug resistance. However, most of these studies have been conducted in vitro. In-depth in vivo studies on the quality control of its crude extracts and active ingredients, as well as on metabolite identification are still very limited. Therefore, more well-designed preclinical and clinical studies are needed to confirm the reported therapeutic potential of I. rubescens.