Manisha Lalan

Poor aqueous solubility severely limits the brain delivery of paliperidone palmitate (PP), necessitating formulation strategies. Here, a docking‐guided approach is employed to engineer intranasal mixed micelles for improved intranasal delivery and potential brain targeting. Molecular docking identifies D‐α‐tocopheryl polyethylene glycol succinate (TPGS) as the primary interacting excipient (ΔG = −4.0 kcal mol ⁻¹ ), while Tween 80 provides complementary interactions enabling cooperative micellization. The optimized PP‐loaded mixed micelles (PP‐MM), developed via a 3 ² factorial design, exhibit nanoscale size (14.97 ± 0.82 nm), narrow dispersity (PDI 0.270 ± 0.021), and efficient drug loading (4.1 ± 0.27%). The formulation demonstrates markedly enhanced in vitro release (89.3 ± 8.2% vs. 33.8 ± 2.8% at 360 min) and substantially improved ex vivo nasal permeation (66.30 ± 5.32% vs. 21.40 ± 2.21%), achieving a 2.64‐fold increase in steady‐state flux (compared to drug suspension). In vivo pharmacodynamic evaluation shows superior suppression of ketamine‐induced hyperlocomotion (279.16 ± 18 vs. 448.33 ± 21.60 counts) without detectable neurotoxicity, supported by preserved neuronal architecture. Collectively, these findings establish docking‐guided mixed micelle engineering as a robust and translational strategy to enhance solubilization, mucosal transport, and therapeutic efficacy, supporting further investigation of this scalable, non‐invasive platform for intranasal delivery of poorly soluble antipsychotic agents.

The MYC proto-oncogene is one of the most extensively dysregulated transcription factors in cancer, governing cell cycle progression, metabolic adaptation, and immune evasion. Despite its central role in tumor biology, MYC has been considered an undruggable target due to its nuclear localization, lack of enzymatic activity, and involvement in transcriptional regulation. The emergence of B-cell based immunotherapies has reshaped the understanding of tumor immunology, revealing that B cells exert both effector and regulatory roles in tumor microenvironment. The intersection between MYC biology and B-cell function is relevant, as MYC is indispensable for B-cell maturation and is frequently dysregulated in B-cell-derived malignancies such as Burkitt lymphoma and diffuse large B-cell lymphoma. We focus specifically on the intersection between MYC-driven oncogenic signaling and emerging B-cell-based immunotherapeutic platforms. This review proposes a conceptual reference framework in which MYC is considered not only as a proliferative driver but also as an immune-modulating oncogene that can aid in the design of humoral therapeutic strategies. Therapeutic strategies to inhibit MYC are systematically discussed, including BET and CDK inhibitors, disruption of MYC–MAX dimerization, RNA-based technologies, synthetic lethality approaches, and emerging PROTACs. Cloned B-cell populations, effector B-cells secreting intrabodies, CAR-B platforms, and antibody-based intracellular targeting are areas of focus. An overview is presented of preclinical and clinical advances made thus far, as well as challenges to the successful translation of these therapies for use in patients including tumor heterogeneity, limitations associated with delivery of agents, and risk of inducing autoimmunity. Forecasting the future provides rationale for combining MYC-targeting agents with immunotherapies and using personalized neoantigen-driven B-cell immunotherapies to treat patients with cancer. Overall, these findings support the concept that MYC B-cell-directed strategies will represent a novel means of treating patients with cancer through their development into new classes of therapeutics.

Introduction: Multidrug resistance, inadequate tumor penetration, and systemic toxicity significantly limit the effectiveness of conventional chemotherapy in solid tumors. Scaffold-based localized chemotherapy offers a promising approach to overcome these challenges by delivering drugs directly to the tumor site with sustained and controlled release. Methods: This article reviews electrospun nanofiber scaffolds, injectable hydrogels, 3D-printed scaffolds, and composite biomaterial scaffolds engineered from biodegradable and bioresponsive polymers such as PLGA, PCL, chitosan, and hyaluronic acid. The influence of drug incorporation strategies, including surface loading, encapsulation, and post-fabrication soaking, on drug loading capacity, degradation behavior, mechanical strength, and release kinetics is examined. Results: Preclinical studies in breast cancer, glioblastoma, colorectal cancer, and pancreatic cancer demonstrate that scaffold-based systems increase local drug concentration, reduce systemic toxicity, and improve therapeutic outcomes. Advanced systems such as dual-drug platforms, stimuliresponsive constructs, and immunomodulatory scaffolds show additional potential to modulate the tumor microenvironment, prevent recurrence, and enhance antitumor immune responses. Moreover, technologies such as electrospinning are well established, whereas advanced modalities like 4D bioprinting remain in early developmental stages, limiting their current translational readiness. Discussion: The application of scaffolds in cancer therapy highlights their theranostic potential, combining controlled chemotherapeutic delivery with capabilities for tissue support, microenvironment modulation, and functional integration with biological systems. Conclusion: Nanostructured polymer scaffolds represent a promising strategy for localized chemotherapy in solid tumors. By overcoming key limitations of systemic drug delivery, these platforms enhance treatment precision, improve patient outcomes, and demonstrate strong translational potential for next-generation oncology therapeutics.

The incidence of central nervous system (CNS) disorders is rising globally, particularly as the prevalence of neurodegenerative diseases increases. The primary challenge in such cases is limited transport of therapeutics through the blood-brain barrier (BBB). Statins, widely used for hypercholesterolemia, exhibit pleiotropic neuroprotective effects; however, their therapeutic potential in CNS disorders is restricted by poor brain bioavailability with conventional routes. Intranasal (IN) delivery has long been recognized as a plausible pathway for brain targeting. This narrative review critically examines preclinical literature on IN nanocarrier-based delivery systems developed specifically for statins, with emphasis on nose-to-brain transport, formulation strategies, pharmacokinetics (PK), and neuroprotective outcomes. Novelty and Contribution: This work uniquely integrates a formulation-centric comparison of IN nanocarriers for statins. It highlights the potential of IN delivery, discussing the influence of carrier type, physicochemical properties, and delivery strategy on brain targeting efficiency and therapeutic relevance across different neurological indications. IN nanocarrier systems display potential to enhance statin brain delivery by bypassing the BBB and first-pass metabolism. Nevertheless, current evidence is predominantly preclinical, with significant variability in study design, pharmacokinetic reporting, and safety evaluation. Translation to clinics will require standardized nose-to-brain metrics, long-term safety studies, scalable manufacturing processes, and early regulatory alignment.