Xinyue Zhang is a final-year PhD Candidate in the Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, the University of Hong Kong. Xinyue earned her bachelor's degrees in Clinical Pharmacy from Tianjin University of Traditional Chinese Medicine and in International Pharmacy from the University of Nottingham. She then completed her master's degree in Experimental Pharmacology and Therapeutics at University College London. She is now pursuing a PhD under the supervision of Associate Professors Prof. Aviva Chow and Prof. George Leung, with the financial support of the Postgraduate Scholarship.
Her research focuses on nanoparticle-based drug delivery systems and translational studies on pharmaceutical sciences, with particular emphasis on nano-embedded microparticles as a nose-to-brain therapeutic strategy for central nervous system disorders. She has presented her work at AAPS PharmSci 360 conference in 2023 and has authored or co-authored three peer-reviewed publications in esteemed journals such as Drug Delivery and Translational Research and International Journal of Pharmaceutics.
Nose-to-brain delivery of lemborexant nano-embedded microparticles dry powders for insomnia management
Insomnia, a prevalent condition, affects approximately 30% of the global population. This disorder not only leads to symptoms such as fatigue, cognitive impairment, memory deficits, and mood swings but also raises the risk of developing more serious conditions like mental health disorders, strokes, and cardiovascular diseases. Common pharmacological interventions for insomnia include benzodiazepine receptor agonists, melatonin receptor agonists, and histamine receptor antagonists, albeit associated with adverse effects such as drowsiness and ataxia, particularly in the elderly. Dual orexin/hypocretin receptor antagonists represent a newer class of medications with potential advantages due to their minimal side effects and promising efficacy. Lemborexant, a dual orexin receptor antagonist approved by the FDA in 2019 for insomnia treatment, promotes rapid onset and maintenance of sleep throughout the night. Clinical trials have shown that lemborexant is well-tolerated, especially among elderly individuals with insomnia, also with minimal drug-drug interactions compared to other classes of drugs. It is worth noting that this medication is administered orally, which can be inconvenient and may lead to low compliance among patients, particularly the elderly. Furthermore, it typically reaches peak concentration within 1-3 hours after dosing, varying based on the dosage used in clinical settings. Therefore, there is a need to further accelerate the onset of the drug's effects.
The delivery of drugs encapsulated in nanoparticles in dry powder form through the nose-to-brain technique offers numerous advantages. Nose-to-brain drug administration is increasingly appealing due to its direct access to the central nervous system, minimal invasiveness, enhanced efficacy, reduced side effects, and user-friendliness. Research suggests that drugs can rapidly reach the brain within 15 minutes of intranasal administration. Integrating intranasal delivery with nanotechnology further enhances the potential of this approach, as nanoparticles can prolong drug residence time, enhance cellular absorption, and minimize degradation risks. Compared to nasal sprays, nasal powders provide unique benefits such as extended retention time, improved stability against enzymatic degradation in the nasal cavity, and targeted delivery to the nasal region through the tailored size of dry powder particles.
This proposal seeks funding for the development of lemborexant nano-embedded microparticles in dry powders through the nose-to-brain method for the treatment of insomnia.
Phase 1
To fabricate and optimize lemborexant nanosuspension with suitable particle size, physical stability and Polydispersity index.
Phase 2
To develop lemborexant nano-embedded microparticles in dry powder form from the nanosuspension, aiming to exhibit ideal characteristics for nose-to-brain delivery.
Phase 3
To evaluate the safety of the optimized dry powder in cytotoxicity studies with nasal and brain cell
Self-introduction
I am a third-year PhD student in the Department of Pharmacology and Pharmacy at the University of Hong Kong under the tutelage of Professor Aviva Chow. During my doctoral studies, I have developed extensive expertise in drug delivery research, with a particular focus on nanomedicine. My research centers on the development of nano-embedded microparticles for nose-to-brain drug delivery, a promising therapeutic strategy for brain-related diseases. Notably, my work has led to the successful fabrication of fingolimod nano-embedded microparticles as neuroprotective therapy for ischemic stroke, demonstrating significant neuroprotective effects in an animal model of ischemic stroke. This research has resulted in the publication of a first-author original research articles in the Drug Delivery and Translational Research. My research experience in the field has also helped me to contribute a first-author review article published in the International Journal of Pharmaceutics.
The Proposed Project: Background and Long-term Impacts
Insomnia is a prevalent condition affecting up to 30% of the global population, with profound implications for mental health and overall well-being. Current treatments often fall short in offering rapid onset, ease of use, and minimal side effects, highlighting the need for innovative therapeutic strategies. This project aims to formulate lemborexant, a dual orexin receptor antagonist, into nanostructured dry powder for nose-to-brain delivery. This approach could address the existing challenges of oral administration in insomnia management. The experimental design for this project builds from my published research work, supporting the technical feasibility and ensuring the likelihood of project success. The key anticipated outcomes include improved sleep onset, enhanced sleep maintenance, and reduced next-morning residual sleepiness compared to current treatment options. Furthermore, this project has the potential to establish a robust nose-to-brain drug delivery platform, providing valuable insights for researchers exploring efficient and rapid brain-targeted therapies. It is believed our platform could set the stage for addressing a wide range of brain-related diseases and accelerate the translation of more drugs into clinical applications.
My Next Step in Career Development
This project aligns with my long-term career goal of becoming an independent researcher specializing in advanced drug delivery systems, particularly in the development of innovative nose-to-brain nanotherapy. The project success will not only further refine my research capabilities in conducting nose-to-brain research but also contribute to the preparation of high-quality research manuscripts intended for publication in leading scientific journals. Receiving the DDL Career Development Grant will provide critical support for this project, enabling the purchase of lemborexant and other excipients for the development of nano-embedded dry powder formulations, as well as facilitating the cell studies. This opportunity will position me to make meaningful contribution to the field and advance my career in academia or industry. By judiciously allocating resources to participate in the DDL conference, I aim to present my research on a global stage, forge connections with fellow researchers, and lay the groundwork for substantial career progression.