Journal of Applied Pharmacology and Toxicology

AI-DRIVEN PRECISION MEDICINE IN NEUROPHARMACOLOGY: REVOLUTIONIZING TREATMENT AND GUIDANCE FOR NEUROLOGICAL DISORDERS

2026-09-18T01:28:19-04:00

Background: Neurological disorders represent one of the most pressing and complex challenges in modern medicine, affecting hundreds of millions of individuals globally and imposing an enormous burden on healthcare systems. Traditional pharmacological approaches, while effective for some patients, are often limited by inter-individual variability in drug response, adverse effects, and the intricate pathophysiology underlying conditions such as Alzheimer’s disease, Parkinson’s disease, epilepsy, multiple sclerosis, and major depressive disorders. The emergence of artificial intelligence (AI) and machine learning (ML) as transformative tools in biomedical research has opened unprecedented avenues for precision medicines in neuropharmacology. This paper reviews the current landscape of AI-driven approaches for identifying neurological drug targets, predicting therapeutic outcomes, optimizing treatment regimens, and discovering novel neuroactive compounds. We further discuss the integration of multi-omics data, neuroimaging biomarkers, and electronic health records (EHRs) within AI frameworks, highlighting both the promising advances and the formidable challenges-including data privacy, algorithmic bias, and regulatory considerations- that must be addressed to realize the full clinical potential of AI-driven precision neuropharmacology. Objectives: This comprehensive review systematically examines the current landscape, principal methodologies, clinical applications, and translational challenges of AI-driven precision medicine in neuropharmacology, with a focus on Alzheimer’s disease (AD), Parkinson’s disease (PD), epilepsy, multiple sclerosis (MS), stroke, psychiatric disorders, and rare neurological conditions. Results and conclusions: AI methodologies- including supervised and unsupervised learning, deep learning architectures, graph neural networks, generative models, reinforcement learning, natural language processing, and federated learning- are delivering transformative advances across drug target identification, de novo molecular design, virtual screening, drug repurposing, neuroimaging biomarker analysis, and pharmacogenomics.

EXPLOITING RECEPTOR NANOCLUSTERS TO BIAS CLATHRIN VS. CAVEOLIN UPTAKE: MOLECULAR DESIGN RULES FOR TARGETED ANTI-CANCER NANOMEDICINES

2026-09-18T02:33:33-04:00

Targeted nanomedicine has advanced beyond cell-specific binding toward the deliberate programming of cellular entry pathways. A central determinant of endocytic pathway selection is receptor nano-clustering, a dynamic process governed by multivalent ligand interactions, membrane lipid organization, and cytoskeletal constraints. This work outlines molecular design principles for engineering nanoparticles that bias uptake toward clathrin-mediated or caveolin-mediated endocytosis. Evidence across model systems suggests that nanoparticles in the 30-80 nm size range with moderate-to-high ligand densities (~10-100 ligands per particle or ~0.01-0.1 ligands nm⁻²) typically promote receptor aggregation sufficient for clathrin-mediated endocytosis (CME) through adaptor protein recruitment and progressive membrane curvature. Particles of approximately 50-150 nm, particularly those presenting lower-to-intermediate ligand densities (~0.001-0.05 ligands nm⁻²) and broader spatial ligand separation, more frequently engage caveolin-mediated endocytosis (CvME) within cholesterol-rich membrane domains, facilitating intracellular delivery while reducing lysosomal exposure. Beyond size and ligand density, nanoparticle shape, ligand spacing (~10-30 nm inter-ligand distance), and receptor-ligand residence time collectively regulate clustering geometry and pathway stability. Clathrin-mediated uptake supports efficient internalization but often directs cargo toward degradative endo-lysosomal compartments; caveolin-associated entry may preserve the integrity of sensitive therapeutic payloads. Integration of quantitative imaging, computational modeling, and microenvironmental factors enables predictive control over intracellular trafficking. These insights establish receptor nano-clustering as a tunable design variable for optimizing therapeutic delivery and achieving pathway-selective enhancement of anti-cancer nanomedicines.

PHARMACOLOGICAL ACTIVITIES AND THERAPEUTIC APPLICATIONS OF CISSUS QUADRANGULARIS IN HEALTH AND DISEASE: COMPREHENSIVE REVIEW

2026-09-17T11:36:42-04:00

Background: Cissus quadrangularis, a perennial medicinal plant widely known as Veld grape or Hadjod, has been extensively utilized in traditional Ayurvedic medicine for its diverse therapeutic properties. In recent years, it has attracted considerable scientific interest because of its broad spectrum of pharmacological activities and its potential role in managing various health conditions. Methodology: We conducted a systematic literature review using electronic databases, including PubMed, Scopus, and Google Scholar. We identified relevant studies on the pharmacological activities of C. quadrangularis using appropriate keywords. This review included both preclinical (in vitro and in vivo) and clinical studies. We critically analyzed and synthesized the data to understand the plant's mechanisms of action and therapeutic applications. Results and Discussion: The findings reveal that C. quadrangularis exhibits multiple pharmacological activities, including bone healing, anti-obesity, anti-ulcerative, anti-diabetic, antioxidant, and gastroprotective effects. These activities are primarily attributed to its rich phytochemical profile comprising flavonoids, triterpenoids, and phytosterols. Experimental and clinical evidence supports its traditional uses, particularly for bone regeneration and metabolic disorders. Despite promising outcomes, variations in study design and a lack of large-scale clinical trials highlight the need for further mechanistic and standardized investigations. Conclusion: Cissus quadrangularis demonstrates significant therapeutic potential as a multifunctional medicinal plant. Its integration into modern healthcare systems could offer novel and effective strategies for managing various diseases. However, further well-designed clinical studies are essential to validate its efficacy, safety, and optimal therapeutic applications.

CUBOSOMES AS VERSATILE LIPID NANOCARRIER: STRUCTURAL BASIS, PREPARATION STRATEGIES, BIOMEDICAL APPLICATIONS, AND EMERGING TRENDS

2026-09-18T04:10:49-04:00

Background: Cubosomes are lipid-based nanocarriers with a bicontinuous self-assembled structure and significant potential for advanced drug delivery applications. Their unique cubic internal configuration, extensive surface area, and potential to encapsulate a wide variety of agents, comprising hydrophilic, lipophilic, and amphiphilic compounds, render them advantageous for improving drug properties such as solubility, stability, loading efficiency, and controlled release. Methodology: These innovative nanocarriers have garnered considerable attention across various biomedical domains, including cancer treatment, antimicrobial and antiviral therapy, transdermal formulations, oral bioavailability enhancement, vaccine delivery, and responsive systems. Results and Discussion: This review outlines the structural features, compositions, stabilization methods, self-assembly theories, drug-encapsulation dynamics, release profiles, preparation techniques, and essential characterization methods of cubosomes. Conclusion: It examines recent advances in biomedical applications targeting different diseases, along with emerging technologies that help clarify the future directions of these nanocarriers.

NANO-PHYTO PUNCTURE: ENHANCING HERBAL BIOAVAILABILITY THROUGH NANOTECHNOLOGY

2026-09-18T08:49:47-04:00

Nano-phytopuncture represents a novel integrative therapeutic strategy that synergizes traditional pharmacopuncture with advanced nanotechnology to overcome the pharmacokinetic limitations of herbal compounds. Conventional herbal extracts used in pharmacopuncture often suffer from poor water solubility, rapid metabolism, and low systemic bioavailability, leading to inconsistent clinical efficacy. Integrating nanocarrier systems such as polymeric nanoparticles, lipid-based carriers (SLNs [Solid Lipid Nanoparticles], NLCs [Nanostructured Lipid Carriers], liposomes), inorganic nanoparticles (gold, iron oxide), and nanogels can significantly improve solubility, stability, targeted delivery, and sustained release of phytochemicals. These carriers enhance lymphatic uptake, utilize passive EPR (Enhanced Permeability and Retention) and active targeting, and enable stimuli-responsive release, thereby improving therapeutic concentrations at target sites while minimizing systemic toxicity. Preclinical studies highlight promising applications in managing cancer, infections, inflammation, neurological disorders, and iron deficiency. However, translational challenges remain, including the need to standardize herbal-nanoformulations, develop GMP-compliant scale-up processes, and conduct rigorous safety and toxicology assessments. Surface modifications such as PEGylation and chitosan coating help reduce immunogenicity and enhance circulation time. Yet, the lack of robust clinical trials and regulatory frameworks specific to these hybrid systems continues to hinder their clinical integration. This review critically evaluates current nanotechnological approaches applied in pharmacopuncture, with emphasis on formulation strategies, mechanisms of enhanced bioavailability, therapeutic efficacy, and translational bottlenecks. This review on nano-phytopuncture offers valuable insights for young researchers engaged in drug discovery and the development of phytonano formulations by bridging traditional herbal therapeutics with cutting-edge nanotechnology. It serves as a comprehensive knowledge platform that explains how nanocarrier systems can be strategically employed to overcome longstanding challenges in herbal pharmacokinetics, such as low bioavailability, instability, and non-specific distribution.

DESIGN, IN SILICO STUDY, SYNTHESIS AND BIOLOGICAL EVALUATION OF BENZOTHIAZOLE-BASED NITROGEN HETEROCYCLE DERIVATIVES AS NOVEL ANTIEPILEPTIC AGENTS

2026-09-18T08:53:06-04:00

Background: This study explores how novel benzothiazole-based nitrogen heterocycles would address drug resistance in epilepsy that occurs in approximately 30 percent of patients. We prepared four new 2-aminobenzothiazole analogs (DD1-DD4) by molecular hybridization and performed comprehensive in silico and in vivo experiments. Methodology: Pharmacokinetic profiling and toxicity predictions indicated that these compounds were highly drug-like, could cross the blood-brain barrier, and appeared to be quite safe. Docking to the human GABA-A homopentamer (PDB ID: 4COF) identified DD3 and DD4 as the best hits in the in silico evaluation, with a binding energy of -7.7 kcal/mol, matching the clinical reference, Riluzole. Results and Discussions: After synthesizing the molecules, we tested their anticonvulsant activity in vivo in a PTZ (Pentylenetetrazole)- induced seizure model in Swiss albino mice. Among the set, DD2 was the most promising, as it had the highest safety margin among all compounds, as shown by an acute toxicity study. Based on the acute toxicity results and highest safety margin, only DD2 was selected for in vivo activity, and it significantly reduced seizure latency and episode duration at higher doses than controls. Conclusion: Overall, these findings indicate that adding nitrogen heterocycles at C-2 of the benzothiazole core fine-tunes interactions with neurological targets. Ultimately, the evidence suggests that DD2, DD3, and DD4 are viable leads to develop next-generation antiepileptic drugs that would be more effective in controlling drug-resistant seizures.