Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder characterized by persistent airflow limitation and chronic airway inflammation. Current therapeutic strategies primarily offer symptomatic relief and are often limited by systemic side effects, inadequate lung deposition, and poor patient compliance. Naringin (NAR), a natural flavonoid with strong antioxidant, anti-inflammatory, and anti-fibrotic activities, has demonstrated potential in mitigating COPD-associated pathophysiology. However, its therapeutic application is restricted by poor water solubility, low bioavailability, and rapid metabolism. Nanotechnology-based drug delivery systems, particularly poly(lactic-co-glycolic acid) (PLGA) nanoparticles, provide an effective approach for lung-targeted therapy. Their nanoscale size promotes deep lung deposition, enhanced cellular uptake, reduced lung clearance, improved therapeutic efficacy, and reduced systemic side effects. The present study aimed to develop NAR-loaded PLGA nanoparticles (NAR PLGA NP) for enhanced cell-targeting in inflammatory lung conditions. NAR PLGA NP were prepared using the emulsion solvent evaporation method, with PLGA in the organic phase and soya lecithin (SL) with poly(vinyl alcohol) (PVA) as surfactants in the aqueous phase. A face-centered central composite design was employed to optimize the formulation. The optimized nanoparticles were characterized for size distribution by dynamic light scattering, entrapment efficiency, Transmission Electron Microscopy (TEM), Fourier Transform Infrared (FTIR), Differential Scanning Calorimetry (DSC), X-Ray Diffraction (XRD), and in vitro drug release. The safety of PLGA and lecithin-coated PLGA nanoparticles (LC PLGA NP) was assessed using an MTT assay on lung epithelial cells, followed by cellular uptake studies, angiogenesis by chick Yolk Sac Membrane (YSM) assay, and in vitro evaluation of reactive oxidative stress (ROS) and anti-inflammatory activity. The optimized PLGA formulation showed a hydrodynamic diameter of 201 ± 1 nm with PDI 0.20 ± 0.03 and EE of 76.11 ± 2.1%, and 81.7 ± 4.9% drug release at 72 h, whereas LC PLGA NP showed a hydrodynamic diameter of 308 ± 3 nm, PDI of 0.21 ± 0.05, entrapment efficiency of 82.45 ± 4.8%, and 71.4 ± 3.2% drug release at 72 h. Both PLGA NP and LC PLGA NP demonstrated good cytocompatibility with lung epithelial cells, efficient cellular uptake, and a significant reduction in intracellular reactive oxygen species (ROS) levels (**** p value < 0.0001). Moreover, the formulations markedly suppressed pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β, indicating anti-inflammatory activity. The angiogenesis assay further suggested their ability for lung tissue repair and remodeling. These findings support the potential of LC PLGA NP as a promising cell-specific targeting system for naringin in inflammatory lung conditions.

In situ photo-vaccination (ISPV) is a promising cancer immunomodulation strategy that combines photodynamic therapy (PDT) with targeted release of chemotherapy to transform tumors into personalized vaccines. However, its efficacy in controlling established, larger distal tumors remains limited, reflecting a significant challenge among therapeutic cancer vaccines. To address this, we used a bilateral Colon 26 murine tumor model to systematically optimize ISPV parameters, including drug-light interval, paclitaxel prodrug dose, light dose, size of the illuminated tumor (related to antigen dose), and checkpoint blockade, and to link these to cellular mechanisms of immunogenic cell death. A low prodrug dose (0.5 μmol/kg compared to ~24 μmol/kg of Paclitaxel in mice) and a fluence rate of 75 mW/cm2 for 30 min with a 30-min drug-light interval produced the strongest systemic responses. Abscopal efficacy was strongly linked to antigen dose: treating larger primary tumors expedited control of distant tumors, allowing the suppression of untreated tumors to a size comparable to the primary tumor. Checkpoint inhibition with anti-CTLA-4 was essential, as its removal eliminated distant tumor control. Importantly, optimized ISPV reproducibly controlled distant tumors of a size equivalent to the treated primary, an outcome rarely achieved with other in situ vaccination approaches. These findings establish a mechanistically informed framework for PDT-driven ISPV and provide a strong rationale for translation of this strategy to the treatment of metastatic cancer.

pH-responsive polymers represent a transformative class of smart materials that adapt their physicochemical properties in response to environmental pH changes. This dynamic behavior enables precise control over drug release, tissue interaction, and diagnostic performance, making them highly relevant for advanced healthcare applications. These polymers exploit ionizable functional groups that undergo protonation or deprotonation, triggering conformational changes, solubility shifts, or swelling behavior. Such responsiveness is particularly advantageous in physiological contexts where pH gradients exist, such as the gastrointestinal tract, tumor microenvironments, and intracellular compartments. Recent advances have expanded their utility from simple drug carriers to multifunctional platforms integrating targeting, imaging, and therapeutic functions. Innovations in polymer design, such as block copolymers, hydrogels, and nanostructured assemblies, have improved biocompatibility, tunability, and responsiveness, enabling controlled delivery of small molecules, proteins, and nucleic acids. Furthermore, hybrid systems combining pH-sensitive polymers with inorganic or biological components have opened new avenues for personalized medicine and regenerative therapies. Despite significant progress, challenges remain in achieving predictable in vivo performance, scalable synthesis, and regulatory compliance. This review critically examines the molecular mechanisms, material architectures, and biomedical applications of pH-responsive polymers, highlighting emerging trends and future directions. By bridging chemistry and clinical needs, these adaptive materials are poised to revolutionize therapeutic strategies and diagnostic technologies in modern healthcare.

Gastrointestinal inflammation is a multifaceted condition deeply connected to the gut microbiota. The prebiotics, probiotics, synbiotics and their metabolites, termed postbiotics, have been explored extensively in the past as a novel approach in managing inflammatory bowel disorders. Prebiotics, probiotics, and postbiotics derived from food sources play crucial roles in modulating the gut microbiota and significantly impact gastrointestinal inflammation. Prebiotics are non-digestible, selectively fermented dietary fibers found in foods such as inulin-type fructans and galacto-oligosaccharides that promote the growth of beneficial gut bacteria like bifidobacteria and lactobacilli. These prebiotics contribute to the production of short-chain fatty acids which possess anti-inflammatory properties and enhance immune regulation in the gut. Together, prebiotics, probiotics, and postbiotics synergistically maintain and restore gastrointestinal health by modulating the gut microbiome composition, enhancing production of anti-inflammatory metabolites, strengthening the intestinal barrier, and regulating immune responses. These interventions show promise in preventing and managing gastrointestinal inflammatory conditions such as irritable bowel syndrome, Crohn's disease, and ulcerative colitis by counteracting dysbiosis and mucosal inflammation. Drawing from recent preclinical and clinical studies, these strategies have shown promising results in managing gastrointestinal inflammation. Despite the compelling evidence, significant challenges remain. These include the considerable variability of host responses, the necessity for standardized strains and precise dosages, and a lack of a unified regulatory framework. This comprehensive review integrates the current understanding of prebiotics, probiotics, synbiotics, and postbiotics, highlighting their mechanistic interplay and highly promising role in managing gastrointestinal inflammation. It provides an in-depth discussion on current limitations and future directions for research and clinical application.

The present investigation aimed to formulate and optimize sustained release proliposome dry powder for inhalation of Voriconazole (VZ) and its in vitro and in vivo evaluation. The proliposome-based dry powder for inhalation was formulated by spray drying technique using Phospholipon 90H and cholesterol in the lipid phase, mannitol as a carrier, and L-leucine as a dispersing agent. A face-centered central composite design was used to study the influence of factors on responses, vesicle size, VZ entrapment efficiency, and drug release. The optimized formulation was further characterized by FTIR, FESEM, DSC, XRD, and evaluated for in vitro drug release, in vitro aerosol deposition, and in vivo lung retention study in Wistar rats. For the optimized batch F-5 proliposome formulation, vesicle size was observed as 191.7 ± 0.049 nm with PDI 0.328 ± 0.009, entrapment efficiency as 72.94 ± 0.56%, and cumulative drug release after 8 h of dissolution was 82.0 ± 0.14%. The median mass aerodynamic diameter (MMAD) generated by optimized formulation F5 was significantly lower (3.85 ± 0.15 µm, p < 0.0001) as compared to spray-dried voriconazole (SD-VZ) (8.35 ± 0.23 µm). In vivo studies demonstrated a profound enhancement in lung retention (3.8-fold) compared to SD-VZ and oral VZ dispersion. Conclusively, proliposome formulation of voriconazole is a plausible and convincing approach for pulmonary fungal infections, considering its sustained release behaviour and prolonged lung retention.

Mesenchymal stem cells (MSCs) contribute significantly to wound healing due to their ability to self-renew, modulate immune responses, and differentiate into various cell types. However, challenges such as unpredictable growth, limited vascular transport efficiency, stringent storage and maintenance requirements that limit the widespread clinical use of MSC-based therapy, highlighting the need for developing effective cell-free alternatives. The regenerative effects of MSCs are mediated through paracrine signaling, primarily via their secretome, which includes extracellular vesicles and soluble factors, especially exosomes. Compared to MSC therapy, exosomes provide superior benefits in terms of storage, safety, and efficiency in targeting the wound sites due to their enhanced tissue penetration capabilities. However, a specific aspect that remains underexplored in exosome-based therapy for wound healing is the development of optimized delivery systems, to ensure controlled, sustained release and precise localization of the exosomes at the wound sites. This review uniquely focuses on this critical and emerging area, providing a detailed overview of the current advancements and limitations in exosomes-based wound healing therapies, with a focus on their delivery strategies. The insights presented in this review are expected to accelerate the development of innovative, effective treatments, revolutionizing wound care management and advancing regenerative medicine in clinical practice.

Quercetin, a flavonoid, has well-proven cytotoxicity potential, but its therapeutic efficacy is hampered by hydrophobicity, stability issues, and lower bioavailability. The present research aims to address these issues and formulation barriers by formulating a quercetin-loaded micellar nanogel. Quercetin was encapsulated in PF 68 micelles to enhance its solubility, loading, and stability to better its therapeutic potential. The nanogel was further characterized regarding for pH, spreadability, and in vitro cytotoxicity against human breast cancer cells (MCF-7). The resulting micelles exhibited a particle size of 180.26 ± 2.4 nm, surface charge of −13.5 mV, entrapment efficiency of 78.4 ± 1.2%, and in vitro release of 96.11 ± 0.75% up to 8 h. This in vitro cytotoxicity study on MCF-7 cell lines reveals the improved TGI and GI 50 values of micellar nanogel formulation compared to quercetin. The overall study results demonstrated that the developed micellar nanogel system might serve as a promising nanocarrier to enhance the cytotoxic potential of quercetin in cancer therapy.

INTRODUCTION:Burn wounds are painful injuries that demand immediate and effective management. Conventional wound care solutions often have limitations, such as discomfort during application or removal and potential damage to healing tissue. Therefore, developing novel wound dressings that support biological processes and promote wound healing is highly beneficial. Electrospun nanofibers have emerged as a promising platform for the development of biomedical wound dressings due to their unique structural and functional properties. This study evaluates the burn wound healing potential of electrospun nanofibers composed of aloe polysaccharides, sodium alginate, and Polyvinyl Alcohol (PVA), impregnated with Silver Nanoparticles (AgNPs). METHOD:AgNPs were synthesized using a green approach, employing Aloe vera as a reducing agent. Characterization of AgNPs was performed using UV-vis spectroscopy, FTIR, zeta potential analysis, and TEM. Aloe polysaccharides were extracted using ultrasonication and characterized via FTIR, XRD, and DSC. The extracted polysaccharides were then blended with PVA and sodium alginate to fabricate electrospun nanofiber sheets, into which the synthesized AgNPs were incorporated and analyzed for antibacterial, angiogenesis, and in vivo studies. RESULTS:AgNPs exhibited spherical morphology with sizes ranging from 20 to 27 nm under TEM. Electrospun nanofiber sheet displayed a uniform structure with an average fiber diameter of 129 nm, as confirmed by SEM analysis. A sustained release of silver ions (78.98 ± 0.61% over 48 hours) was observed. The nanofibers exhibited strong antibacterial activity against Escherichia coli and Staphylococcus aureus, promoted angiogenesis, and significantly enhanced wound healing in a burn wound model. DISCUSSION:AgNPs impregnated nanofiber sheet exhibited superior wound healing, angiogenesis, and antibacterial properties ideal for wound healing applications. The nanofiber sheets mimicked the extracellular matrix and supported angiogenesis. Enhanced wound closure in vivo studies confirmed the therapeutic potential of the nanofibers. CONCLUSION:AgNPs-impregnated nanofiber sheets offer antibacterial activity and support angiogenesis, suggesting their potential as a multifunctional wound dressing for effective burn treatment.

The lungs serve a critical function in air transport and gas exchange, presenting an appealing route for noninvasive drug administration. However, the unique physiology and anatomy of the lungs influence the efficacy and safety of pulmonary drug delivery. A comprehensive approach combining both an optimized pharmaceutical formulation and an appropriate delivery device is essential for effective pulmonary therapies. Pulmonary drug delivery can achieve both local and systemic effects. During pulmonary drug delivery, several factors viz. particle size, electrostatic charge, inhalation parameters, airway functionality, disease state, and proper use of delivery device must be considered. Current advancements in nanotechnology have led to the development of innovative nanocarriers tailored for pulmonary administration. These nanocarriers offer benefits such as targeted deposition in specific areas of the tracheobronchial tree, controlled drug release, protection of active pharmaceutical ingredients (APIs) from lung clearance mechanisms, and cell-specific targeting. Research on nanomedicine for pulmonary delivery has progressed significantly, resulting in the development of several (nano)formulations, devices, and products in various stages of clinical development, with some already commercially available. Recent studies have focused on improving inhalation device testing, aerosol formulation development, and the application of in vitro, ex vivo, in vivo, and in silico models to better understand pulmonary drug deposition and disposition. This review highlights the anatomical and physiological features of the lungs, recent advances in nanocarrier design and inhalation technologies. In addition, the applications in respiratory and systemic disease management have also been included. While significant progress has been made, challenges remain in optimizing pulmonary drug delivery systems, necessitating further research to address these complexities and enhance the therapeutic outcomes.

Cancer is one of the leading causes of mortality worldwide. Nanomedicines have significantly improved life expectancy and survival rates for cancer patients in current standard care. However, recurrence of cancer due to metastasis remains a significant challenge. Vaccines can provide long-term protection and are ideal for preventing bacterial and viral infections. Cancer vaccines, however, have shown limited therapeutic efficacy and raised safety concerns despite extensive research. Cancer vaccines target and stimulate responses against tumor-specific antigens and have demonstrated great potential for cancer treatment in preclinical studies. However, tumor-associated immunosuppression and immune tolerance driven by immunoediting pose significant challenges for vaccine design. In situ vaccination represents an alternative approach to traditional cancer vaccines. This strategy involves the intratumoral administration of immunostimulants to modulate the growth and differentiation of innate immune cells, such as dendritic cells, macrophages, and neutrophils, and restore T-cell activity. Currently approved in situ vaccines, such as T-VEC, have demonstrated clinical promise, while ongoing clinical trials continue to explore novel strategies for broader efficacy. Despite these advancements, failures in vaccine research highlight the need to address tumor-associated immune suppression and immune escape mechanisms. In situ vaccination strategies combine innate and adaptive immune stimulation, leveraging tumor-associated antigens to activate dendritic cells and cross-prime CD8+ T cells. Various vaccine modalities, such as nucleotide-based vaccines (e.g., RNA and DNA vaccines), peptide-based vaccines, and cell-based vaccines (including dendritic, T-cell, and B-cell approaches), show significant potential. Plant-based viral approaches, including cowpea mosaic virus and Newcastle disease virus, further expand the toolkit for in situ vaccination. Therapeutic modalities such as chemotherapy, radiation, photodynamic therapy, photothermal therapy, and Checkpoint blockade inhibitors contribute to enhanced antigen presentation and immune activation. Adjuvants like CpG-ODN and PRR agonists further enhance immune modulation and vaccine efficacy. The advantages of in situ vaccination include patient specificity, personalization, minimized antigen immune escape, and reduced logistical costs. However, significant barriers such as tumor heterogeneity, immune evasion, and logistical challenges remain. This review explores strategies for developing potent cancer vaccines, examines ongoing clinical trials, evaluates immune stimulation methods, and discusses prospects for advancing in situ cancer vaccination.