Precision Drug Delivery Strategies for Treatment-Resistant Depression: Opportunities and Challenges of FUS-BBBO and Spatial Molecular Profiling

Nanomedicine for epilepsy: Expanding beyond conventional drug targets.

This discussion aims to inspire a reorientation of nanomedicine strategies toward precision therapy for epilepsy by highlighting how emerging nanomedicines are expanding the therapeutic target repertoire to include key non-neuronal nodes, with a focus on neuroinflammation and BBB repair.

Engineering Advanced Nanomedicine Against Depression: From Treatment Challenges to Delivery Strategies.

By moving beyond generic strategies for BBB penetration to address the distinctive pharmacotherapeutic shortcomings of depression, engineered nanomedicine holds great promise for advancing next-generation antidepressant therapies that achieve rapid onset, precise intervention, and comprehensive improvement in patient quality of life.

Multikinase Inhibition as a Therapeutic Strategy for Status Epilepticus: Current Evidence and Future Directions

Status epilepticus (SE) is a serious neurological emergency defined by prolonged or recurring seizures that frequently do not respond to standard antiepileptic medications. Recent revelations into the molecular underpinnings of SE, including neuroinflammation, oxidative stress, angiogenesis, and disruption of the blood-brain barrier, have stimulated research into targeted therapeutics. Lenvatinib, a multi-kinase inhibitor sanctioned for many cancers, has demonstrated potential neuroprotective and anti-inflammatory effects by targeting the VEGFR, FGFR, and PDGFR pathways, which are also involved in epileptogenesis. This review examines the therapeutic potential of repurposing lenvatinib in the pilocarpine- induced status epilepticus model, a well-established preclinical framework that simulates human temporal lobe epilepsy. Preclinical evidence, mechanistic relevance, pharmacodynamics, blood-brain barrier permeability, and safety profiles were reviewed to determine the viability of lenvatinib as an adjunct or alternative therapy. Furthermore, the function of angiogenic signaling in the advancement of seizures and how lenvatinib's multitargeted mechanism may influence critical pathogenic pathways were also examined. Although existing evidence is insufficient, in silico and in vivo investigations indicate that lenvatinib may disrupt neuroinflammatory and vascular alterations essential to SE pathogenesis. Additional preclinical validation is necessary to verify its efficacy and safety. This review seeks to establish a thorough basis for subsequent research on the repurposing of lenvatinib in neurotherapeutics.

Nose-to-Brain Therapeutics in Parkinson’s Disease: Clinical Trials, Mechanisms, and Therapeutic Potential

Background/Objectives: Intranasal delivery is a promising noninvasive approach to enhance central nervous system drug delivery in Parkinson’s disease (PD), potentially bypassing the blood–brain barrier and minimizing gastrointestinal side effects. This review summarizes clinical trials and translational evidence for intranasal PD therapies by treatment options and intent, highlighting key challenges in efficacy, pharmacokinetics, and safety. Methods: We reviewed human clinical trials, preclinical and pilot studies, and pharmacokinetic investigations of intranasal therapies for PD. Comparisons to established treatments were included in context. Only PD-specific clinical studies were analyzed. Therapies were grouped by rescue, antioxidant/metabolic/hormonal, and biologic or cell-based approaches, with continuous-delivery systems reviewed separately. Results: Intranasal rescue therapies, such as apomorphine, provide rapid improvement during OFF episodes (periods when the effects of PD medications fade and symptoms reappear), but tolerability issues and nasal irritation limit usage. Early-phase studies suggest intranasal delivery enables quick symptom relief and favorable pharmacokinetics, though most trials are small and focus on feasibility. New approaches include antioxidants, neurotrophic factors, gene therapy, and cell-based methods, with advanced formulations enhancing nasal retention and brain uptake. However, more translational evidence and long-term safety data are needed. Conclusions: Intranasal therapies for PD offer rapid rescue and expand options beyond standard drugs. Large, well-designed trials are needed to confirm efficacy, long-term safety, and optimal formulations. Intranasal delivery remains an emerging but potentially transformative strategy requiring further clinical research.

Disease mechanisms and translational barriers guide nanocarrier design for nose to brain delivery in Alzheimer’s disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with limited disease-modifying treatment options, partly because many therapeutic agents show insufficient brain exposure and dose-limiting systemic adverse effects after conventional administration. Nose-to-brain (N2B) delivery has emerged as a non-invasive strategy to transport therapeutics to the central nervous system through the olfactory and trigeminal pathways, thereby partially bypassing the blood-brain barrier. Recent advances in nanomedicine and biomaterial engineering have further improved this approach by enhancing drug stability, nasal residence, mucosal transport, and brain-targeting efficiency. This review examines nanocarrier-enabled N2B delivery strategies for AD from a mechanism-guided perspective, highlighting how AD-related pathological processes shape the selection of therapeutic cargos and formulation designs. We discuss recent progress in the intranasal delivery of repurposed small molecules, natural products, insulin-related agents, peptides and proteins, extracellular vesicles, antibodies, and nucleic acid-based therapeutics. We further summarize major nanocarrier and formulation platforms, including lipid-based systems, polymeric nanoparticles, micelles, extracellular vesicles, in situ gels, and device-assisted delivery technologies. Particular attention is given to the design parameters that influence N2B performance, including particle size distribution/PDI, surface charge, mucus interaction, cargo protection, targeting modification, biodistribution, and deposition reproducibility. Finally, we critically evaluate the translational challenges that continue to limit clinical application, including species differences in nasal anatomy, dose-volume restrictions, device-dependent variability, limited human pharmacokinetic evidence, manufacturing complexity, long-term safety, and regulatory requirements. By integrating disease mechanisms, nanocarrier design, and translational considerations, this review provides a structured perspective for developing more rational and clinically feasible N2B nanodelivery systems for AD.

Nose-to-Brain Nanocarriers for Migraine Management: A Comprehensive Review of Drug Delivery Strategies and Translational Challenges.