article · Scientific Reports
Anxiety is a common psychopathology with increased prevalence during the pandemic, yet conventional medications like benzodiazepines carry an unfavourable risk to benefit ratio. Naturally occurring quercetin offers a safer alternative, but its use is limited by low water solubility and poor bioavailability. To overcome these delivery challenges, polymeric nanocapsules loaded with quercetin were developed using a nanoprecipitation method for intranasal administration directly to the brain. The optimal formulation achieved an encapsulation efficiency of over 92 per cent and displayed a biphasic release profile featuring an initial burst followed by sustained release. In behavioural testing, the intranasally delivered nanocapsules outperformed orally and intranasally administered quercetin dispersions. Additionally, the nanocapsule formulation demonstrated a good safety profile with high tolerability, indicating its viability as a delivery platform.
Standard anxiety medications often carry severe side effects and risks, prompting interest in natural compounds like quercetin. However, delivering such compounds effectively to the brain is difficult due to poor solubility. By demonstrating that nasal nanocapsules enhance performance and maintain safety, this approach provides a non-invasive pathway for developing gentler, more effective therapies for mental health conditions.
This work points towards pharmaceutical applications in mental health treatments, specifically for pharmaceutical developers seeking alternatives to traditional anxiolytics. The technology serves as a targeted delivery platform for poorly soluble natural active ingredients. Because the findings are based on formulation development, in vitro release testing, and preliminary behavioural models, the platform remains at an early-stage research phase and requires further translational development before clinical or commercial deployment.
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Anxiety is one of the most prevalent forms of psychopathology that affects millions worldwide. It gained more importance under the pandemic status that resulted in higher anxiety prevalence. Anxiolytic drugs such as benzodiazepines have an unfavorable risk/benefit ratio resulting in a shift toward active ingredients with better safety profile such as the naturally occurring quercetin (QRC). The delivery of QRC is hampered by its low water solubility and low bioavailability. The potential to enhance QRC delivery to the brain utilizing polymeric nanocapsules administered intranasally is investigated in the current study. Polymeric nanocapsules were prepared utilizing the nanoprecipitation technique. The best formula displayed a particle size of 227.8 ± 11.9 nm, polydispersity index of 0.466 ± 0.023, zeta potential of - 17.5 ± 0.01 mV, and encapsulation efficiency % of 92.5 ± 1.9%. In vitro release of QRC loaded polymeric nanocapsules exhibited a biphasic release with an initial burst release followed by a sustained release pattern. Behavioral testing demonstrated the superiority of QRC loaded polymeric nanocapsules administered intranasally compared to QRC dispersion administered both orally and intranasally. The prepared QRC loaded polymeric nanocapsules also demonstrated good safety profile with high tolerability.
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DOI: 10.1038/s41598-023-27665-6
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