The blood-brain barrier (BBB) is an obstacle to effective therapy in neurological disease because it restricts drug access to the brain. Borneol, a lipophilic bicyclic monoterpene used in traditional Chinese medicine, has been associated with opposing effects on BBB function: barrier integrity restoration in ischaemic stroke models and barrier permeability enhancement in drug-delivery models. This mini-review evaluates whether these findings represent a true contradiction or a context-dependent pattern of BBB modulation. The impact of borneol treatment on the intact and damaged barrier was compared by aligning matched readouts within the physical and selective barrier phenotype categories. For example, physical barrier integrity measures explored ionic permeability, tight junction (TJ) organization and macromolecular leakage and selective barrier function measures assessed transcytosis and transport related outcomes. Molecular markers of endothelial state and extracellular matrix integrity were also compared. Across stroke models, borneol was consistently associated with improved barrier resistance, junctional structure preservation and reduced pathological leakage, with the major facilitator superfamily domain-containing protein 2a (Mfsd2a) and caveolin-1 (Cav-1)-mediated transcytosis representing the most clearly defined downstream mechanistic pathway. In delivery models, borneol was associated with transient TEER reduction, TJ protein (claudin-5) redistribution and enhanced tracer or payload passage, consistent with reversible barrier loosening. When these findings were compared through matched readouts, these differences became less contradictory and more conditionally structured. Overall, borneol is better understood as a context-sensitive modulator of BBB function rather than a uniformly barrier-opening or barrier-protective agent. However, translation remains limited by substantial heterogeneity in model, dose and timing, together with unresolved upstream mechanisms.
H. N. Shivakumar, Ayush Parmar, Rushikesh Shinde, Sanjana S. P
Oesophageal candidiasis remains challenging to treat owing to rapid transit of conventional oral formulations through the oesophagus, resulting in inadequate local drug delivery and reduced therapeutic efficacy. To address these limitations, the present study aimed to develop fluconazole-loaded chitosan microspheres (FCZ-CMs)-based orodispersible tablets (ODTs) that rapidly disintegrate in the oral cavity while releasing mucoadhesive microspheres capable of adhering to oesophageal mucosa, enabling sustained localized drug delivery. FCZ-CMs were developed by the emulsion cross-linking method using a 2 3 full factorial design to optimize particle size (PS), entrapment efficiency (EE), drug release (DR), and ex vivo oesophageal retention (ORT). Optimised FCZ-CMs (F9) were extensively characterized by Infrared spectroscopy (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffractometry (XRD), and in vitro drug release studies. Further, the ODTs developed by direct compression of F9 were evaluated for wetting time (WT), disintegration time (DT), drug content (DC), % drug release at 60 min (%DR), similarity (f 1 /f 2), and stability under real-time and accelerated conditions. The optimised FCZ-CMs (F9) exhibited a PS (31.81 ± 1.14 μm), EE (84.12% ± 2.15%), DR (58.46% ± 1.89% at 60 min), and ORT (51.22% ± 2.11% at 30 min), demonstrating excellent suitability for localized oesophageal delivery. FTIR confirmed drug–polymer compatibility, SEM revealed spherical microspheres with a crenated surface morphology favourable for mucoadhesion, while DSC and XRD demonstrated reduced crystallinity of FCZ within the chitosan matrix. The ODTs loaded with F9 displayed high DC (99.14% ± 0.58%), short WT (19.62 ± 0.51s), and DT (23.83 ± 0.86s). The dissolution profile of ODTs remained comparable to that of F9 (p > 0.05), with drug release of 53.16% ± 1.24% at 60 min and similarity factor (f 2 = 80) and difference factor (f 1 = 8), confirming that the compression process did not significantly alter the release behaviour of the optimised microspheres. The formulation also remained stable under both real-time and accelerated storage conditions. The optimised ODTs successfully translated the performance of FCZ-CMs into a patient-friendly, oesophageal-targeted drug delivery system without compromising their controlled-release or mucoadhesive characteristics. The use of a simple, reproducible, and scalable direct compression process, together with preservation of microsphere functionality following tablet compression, highlights the translational potential of this platform for localized treatment of oesophageal candidiasis and deserves further clinical investigation.
Hossein Omidian, Kwadwo A. Mfoafo, Luigi X. Cubeddu
Myocardial ischemia-reperfusion injury (MIRI) and post-infarction remodeling are characterized by dynamic oxidative stress that varies across myocardial regions and disease stages. Reactive oxygen species (ROS)-responsive and redox-modulating biomaterials seek to exploit this environment through stimulus-triggered release or degradation, ROS scavenging, targeted delivery, local retention, and stage-specific repair. This review critically evaluates preclinical strategies for MIRI, myocardial infarction, and post-infarction remodeling. Major platform classes differ substantially in mechanism and translational feasibility: injectable hydrogels offer local retention and spatiotemporal control but often require invasive administration; systemic nanoparticles and liposomes enable tissue-, cell-, or organelle-level targeting but require stronger biodistribution and clearance data; nanozymes provide sustained catalytic redox activity but raise persistence and safety concerns; and cell-, nucleic-acid-, or gas-based systems introduce additional manufacturing and regulatory complexity. Mechanistically, redox interaction represents the initiating action, followed by proximal mitochondrial and cell-death regulation, inflammatory modulation, and later effects on angiogenesis, fibrosis, and ventricular remodeling. Although preclinical studies demonstrate cardioprotective and repair-promoting effects, direct cross-platform comparisons remain limited. Translation is constrained by heterogeneous models, inconsistent definitions of ROS responsiveness, incomplete pharmacokinetic and safety characterization, sparse large-animal validation, and limited manufacturing evidence. ROS-responsive cardiovascular biomaterials therefore remain promising but clinically unproven precision-delivery strategies.
Jinxin Zhang, Rumi Khandelia, Bridget Hogg, Ahmad Z. Bahlool, Tom Hodgkinson, Sally-Ann Cryan, John O’Byrne, David J. Brayden
Osteoarthritis (OA) is the major cause of pain and disability worldwide, particularly affecting the knee joint. Although intra-articular (IA) treatments including corticosteroids and hyaluronic acid (HA), are commonly used to manage symptoms, their therapeutic effects are often short-lived, necessitating repeated injections. In this study, HA-coated solid lipid nanoparticles (HA-DXP-SLNs) entrapping with the glucocorticoid prodrug, dexamethasone palmitate (DXP) was developed as dual-function nanocarrier system for IA delivery. Using a scalable microfluidics platform, monodisperse SLNs of ∼90 nm in diameter were produced with high DXP encapsulation efficiency (88%) and loading capacity (6% w/w). In phosphate buffered saline (PBS), DXP-SLNs exhibited a biphasic release profile with an initial burst followed by sustained release of DXP, which was further moderated by HA surface coating. HA coatings of the SLNs enhanced particle stability, shifted particle surface charge from positive to negative, and enabled uptake by patient-derived primary osteoarthritic chondrocytes (hOAAC). Incubation in murine plasma demonstrated enzymatic conversion of DXP to dexamethasone (DEX), which accumulated in plasma over 72 h. HA-DXP-SLNs suppressed prostaglandin E 2 production by LPS-stimulated THP-1 monocytes and by hOAAC more effectively than uncoated DXP-SLNs, while maintaining cell viability. These findings indicate that the HA coating of SLNs contributes to in vitro therapeutic efficacy of the overall SLNs, as well as to particle stabilisation. HA-DXP-SLNs therefore represent a promising nanocarrier for prolonged IA corticosteroid delivery in knee OA, with the potential to reduce the frequency of current IA corticosteroid and HA administration.
