Naringenin (NR) is a plant-based flavonoid with poor aqueous solubility, which is indicated for the treatment of psoriasis due to its strong antioxidant and anti-inflammatory properties. The aim of this study was to evaluate the non-steroidal NR-loaded nanocochleate hydrogel (NR-NC-G) for its skin permeation, safety, and efficacy in the treatment of psoriasis. First, nanoliposomes (NR-LIPO) were prepared and further chelated using calcium chloride to transform them into nanocochleates (NR-NCs). NR-NCs exhibited rolled sheet-like nanosized particles with a hydrodynamic diameter of approximately 160-170 nm, an encapsulation efficiency of 81-82%, and good colloidal stability, as indicated by a zeta-potential of -27 mV. To achieve a local reservoir-like action, nanocochleates were loaded into a hydrogel comprising of combination of Carbopol 934P and sodium alginate. NR-NC-G was characterised for its physical and rheological characteristics, and it exhibited uniform drug loading, long-term stability, and the ability to scavenge reactive oxygen species (ROS), as validated by various antioxidant assays. Furthermore, NR-NC-G reduced cellular ROS levels, nitrate accumulation, and mitochondrial healing ability in a lipopolysaccharide-stimulated RAW264.7 inflammation model, thereby proving its enhanced antioxidant and anti-inflammatory effects. The ex vivo skin permeation and dermatokinetic studies showed that NR-NC-G exhibited high permeation across the excised skin of BALB/C mice. The dermatokinetic studies showed that topical application of NR-NC-G provided 3.43 and 3.34-fold greater Cmax and AUC0-t in the epidermal layer, respectively, compared to the bulk NR solution. Overall, this novel nanoformulation enhances ROS scavenging capacity, improves cellular uptake, enhances skin permeation and retention, and suggests potential applications for treating psoriasis.
Abstract Background Nanorobotic systems represent an emerging and disruptive paradigm in nanomedicine for precision drug delivery, controlled therapeutic release, and minimally invasive biomedical interventions. Recent advances in materials engineering, bioinspired design, and external actuation techniques have greatly improved the functionality, navigation, and targeting capabilities of nanorobots for biomedical applications in recent years. Objectives This review aims to give a comprehensive overview of the major classes of nanorobotic systems, their propulsion mechanisms, biomedical applications, safety considerations, and translational potential in drug delivery and therapeutic interventions. Methods A critical review of recent literature was carried out to evaluate various nanorobotic platforms including DNA‐based, magnetic, catalytic, biohybrid, ultrasound‐driven, light‐responsive and stimuli‐responsive nanorobots. Their composition, propulsion mechanism, functional dynamics and therapeutic performance were studied systematically. Results Nanorobotic systems have shown great potential for targeted drug delivery, site‐specific therapeutic release, enhanced tissue penetration, and improved treatment precision. The comparative analysis has revealed the differences between the nanorobotic platforms in terms of controllability, biocompatibility, targeting efficiency and translational feasibility. However, a number of challenges remain including biodistribution, immune recognition, reticuloendothelial system clearance, long‐term toxicity, biodegradability, large‐scale manufacturing and regulatory approval. Conclusions Nanorobotic systems have shown great potential for targeted drug delivery, site‐specific therapeutic release, enhanced tissue penetration, and improved treatment precision. The comparative analysis has revealed the differences between the nanorobotic platforms in terms of controllability, biocompatibility, targeting efficiency and translational feasibility. However, a number of challenges remain including biodistribution, immune recognition, reticuloendothelial system clearance, long‐term toxicity, biodegradability, large‐scale manufacturing and regulatory approval.
The dengue virus has developed an effective replication mechanism that enables rapid viral replication in human hosts. The use of a molecular bottleneck offers an ideal approach for antiviral intervention, especially when no clinically authorized antivirals are available against dengue. The replication process is challenging due to functional redundancy. One of the core antiviral targets is the viral RNA-dependent RNA polymerase (RdRp), a conserved and essential component of the DENV replication machinery with no mammalian homolog, which represents a promising target for antiviral intervention. This study employed a multi-tiered drug repurposing approach integrating computational screening, high-throughput virtual screening (HTVS), standard precision (SP), and extra precision (XP) molecular docking of SelleckChem FDA-approved Passed Phase I Drug Library compounds against the DENV RdRp (PDB:5K5M), followed by 200 ns molecular dynamics (MD) simulations, free binding energy analysis, free energy landscape (FEL) analysis, and in vitro antiviral validation. From the screening cascade, Proanthocyanidin and Stachyose were identified as lead candidates with Glide XP docking scores of -11.34 and − 13.08 kcal/mol and Molecular Mechanics/Generated Born Surface Area (MM-GBSA) binding free energies of -52.35 ± 5.29 kcal/mol, respectively. These lead candidates established stable interactions with important catalytic and regulatory residues, including Arg729, Thr794, Ser796, Asp664, and Tyr766, indicating their ability to disrupt key polymerase activity. The stability of the candidates was further confirmed by Molecular dynamics simulations based on the minimal variations of RMSD and compactness of the protein compared with the lead structures, which collectively indicated their compatibility with the polymerase allosteric site. Critically, in vitro assays conducted on DENV infected cells confirmed the Proanthocyanidin exhibited potent dose-dependent antiviral activity with IC50 values of 4.26–7.07 µM across DENV serotypes 1–4, with CC50 >100 µM and selectivity indices > 14, indicating a favorable therapeutic window. These findings identify Proanthocyanidin as a promising RdRp-targeting antiviral candidate and demonstrate the value of integrating computational and experimental approaches for dengue drug discovery.
Baicalin (BA) is a potent flavonoid with antioxidant and anti-inflammatory properties; however, its clinical application is limited due to poor solubility and permeability. The present study aimed to develop an innovative baicalin-loaded essential oil-based lipid nanoparticle hydrogel (BA-NP-G) utilising rosemary oil (RO) as both an excipient and a therapeutic synergist for potential use in skin inflammatory disorders. BA-loaded lipid nanoparticles (BA-NPs) were formulated using a low-energy precipitation method. Following experimental optimisation for particle characteristics and encapsulation efficiency, nanoparticles were further embedded into a Carbopol-xanthan gum hydrogel. Characteristic results of BA-NPs, including size (174 ± 2.1 nm), PDI (0.25), ζ-potential (− 30.01 mV), and high entrapment efficiency (up to 69.6 ± 1.1
Antimicrobial resistance (AMR) is a major global health challenge driven by mechanisms such as biofilm formation, efflux pumps, and genetic mutations. Nanoparticulate and fibrous materials have emerged as promising strategies to overcome these limitations through multimodal antimicrobial action and controlled drug delivery. This review highlights recent advances in electrospun nanofibrous systems, including natural and synthetic polymer-based scaffolds, stimuli-responsive nanofibers, and functionalized patches. Nanoparticle-loaded nanofiber systems demonstrate enhanced performance, including bacterial eradication, sustained drug release, and significant biofilm disruption. Multifunctional systems combining antimicrobial, antioxidant, and immunomodulatory properties further show synergism. Emerging innovations, such as piezoelectric and smart sensing systems, enable self-powered antimicrobial activity and real-time infection monitoring with high detection accuracy. The nanostructured systems reported in this review provide a versatile and effective strategy for combating AMR.
Hydroxychloroquine (HCQ) is widely used in management of rheumatoid arthritis. However, its moderate bioavailability and serious systemic adverse effects limit its therapeutic utility for long term administration. A potential way to overcome these limitations is to develop topical dosage form of the drug, based on nanocarriers for better drug permeation. The nanoformulation was developed using biocompatible lipids and optimized using Box-Behnken experimental design. The optimized nanoformulation had a mean particle size of 110 nm, a polydispersity index of 0.11 and an entrapment efficiency of 84%. The formulation was further incorporated into a Carbopol 934 gel and evaluated for in vitro, ex vivo, and in vivo behaviour as well as therapeutic efficacy. Compared to the conventional gel, the nanogel formulation exhibited higher and sustained release of HCQ over a 24-hour period (67% vs 50%), penetrated the skin more readily (66%), and deposited more amount of drug in the deeper layers of skin. The formulation demonstrated significant anti-inflammatory activity, as measured by 76% inhibition of protein denaturation; in vivo efficacy (24% inhibition of paw edema) and good physicochemical for 6 months. Thus, HCQ nanogel formulation represents a promising transdermal drug delivery system for the better management of rheumatoid arthritis.
Biogenically synthesized metal-based nanoparticles have emerged as an attractive alternative to traditional physicochemical methods. The conventional way to prepare metal nanoparticles involves using toxic chemicals as reducing agents and stabilizers, which is tedious to handle and highly detrimental to the environment. Hence, biological synthetic routes for the biosynthesis of metal nanoparticles have been widely explored in recent research. It involves using biological molecules present in organisms, such as bacteria, plants, and fungi, as well as vitamins and enzymes, to reduce, stabilize, and regulate nanoparticle growth. These green-synthesized nanoparticles have demonstrated promising biomedical applications, especially as antibacterial, anticancer, anti-inflammatory, and neuroprotective agents, owing to their superior biocompatibility and surface chemistry. In addition, there is potential to develop therapeutic formulations that leverage the interactions between nanoparticles’ properties and biological systems. This review discusses the mechanisms of biogenic synthetic routes, with a detailed discussion of plant, bacterial, enzymatic, fungal, and vitamin-mediated green synthetic metal-based nanoparticles and their applications in biomedical and drug delivery fields.
In the present study, alginate and chitosan-based liposomes were synthesized for the delivery of carvacrol and cinnamaldehyde to evaluate their therapeutic efficacy against Escherichia coli (MTCC No. 723, strain H-10407, serotype O78:K80:H11, CFA/I + LT+ ST+) infection in broiler chickens. The formulations were prepared using the ionic gelation method and characterized for pH, zeta potential, zeta size, and polydispersity index. FTIR analysis confirmed the presence of characteristic peaks for both polymers and bioactive oils, while SEM images showed uniformly spherical, smooth, and compact vesicles. The encapsulation efficiencies for both formulations were approximately 90–92% and show sustained drug release. Birds were orally challenged with an E. coli broth culture for in vivo therapeutic evaluation. Treatments were administered for five consecutive days post-infection, and evaluations were conducted at onset of diarrhoea and after treatment. Efficacy was evaluated based on faecal E. coli counts, production performance (body weight, feed intake, feed conversion ratio), haematological parameters, biochemical indices, serum cytokine concentrations, histopathological observations. The combination of encapsulated carvacrol and cinnamaldehyde, as well as the antibiotic-treated group, showed marked reductions in faecal E. coli counts and significant improvements in haemoglobin, liver enzyme activities, cytokine levels, H/L ratios, total protein, electrolyte profile, and intestinal damage compared with the disease control group. The findings suggest that a combination of encapsulated carvacrol and cinnamaldehyde formulations can serve as effective alternatives to antibiotics for managing E. coli infection and enhancing gut health in broiler chickens. This approach also suggests an effective approach in addressing the highly important current global crisis of antimicrobial resistance.
INTRODUCTION:Atopic dermatitis (AD) is a recurring and non-contiguous dermatological condition that impacts a huge global population. Pruritus, inflammation, numerous eczematous lesions, and an unpredictable progression are the hallmark characteristics of this dermatological complication. Despite its multifactorial and incompletely comprehended pathophysiology, AD appears from a combined cause of environmental and genetic factors that lead to epidermal barrier integrity, oxidative stress, and immune system imbalance at both the skin and systemic levels. AREAS COVERED:The lipid nanocarrier (LN), referred to as the vesicular system, has become a focal point of interest among researchers striving to develop novel formulations that improve therapeutic efficacy, avoid off-target effects, prevent premature drug degradation, and increase the safety profile of drugs by different surface modification methods. Hence, LNs are categorized into hard-LNs with hardened surfaces and soft-LNs that can alter their size during distribution in the body for delivering both lipophilic and hydrophilic drugs topically. EXPERT OPINION:In the last two decades, numerous clinical studies have clearly shown the therapeutic relevance of specialized LNs and hybrid systems for effectively managing AD and halting its progression with improved quality of patient life, supporting the therapeutic superiority of advanced LN-mediated interventions compared to traditional treatment modalities.
Iron deficiency anemia (IDA) remains a prevalent global health concern, with conventional oral iron supplements often limited by poor bioavailability and adverse effects. In this study, magnetite iron oxide nanoparticles (IONPs) were functionalized with ascorbic acid (IONP Asc) and folic acid (IONP FA) to enhance iron bioavailability and minimize systemic toxicity. The synthesized nanoconjugates exhibited particle sizes of 36.8-91 nm (IONP Asc) and 80.7 nm (IONP FA), with favorable zeta potentials and polydispersity indices, indicating colloidal stability. Structural and chemical characterizations using SEM, FTIR, DSC, and XRD confirmed successful conjugation and spherical morphology. Hemolysis assays demonstrated excellent hemocompatibility, while in vivo administration significantly improved hematological indices, including hemoglobin concentration and red blood cell count. Biodistribution and histopathological evaluations of the liver, spleen, and kidneys revealed no adverse tissue alterations. These findings underscore the potential of IONP Asc and IONP FA as safe and effective nanotherapeutics for the management of IDA.
ABSTRACT Liver diseases (LD) are a global health concern that arises due to limitations of conventional therapies, including low solubility in biological fluids, rapid metabolism, and insufficient hepatic concentrations. However, nanocrystals (NCs) composed of pure active pharmaceutical ingredients (APIs) are emerging as the most effective tool for increasing the solubility, bioavailability, and targeting of poorly soluble drugs for LD. This review summarizes recent advances in the design, processing, and application of NCs for LD. The review focuses particularly on comparing top‐down, bottom‐up, and combined processing methods, with special consideration given to API‐specific requirements as a drug selection criterion for NCs, the choice of stabilizers, and the application of NCs in LD. The idea is to present polysaccharide‐based, inorganic, and drug NCs for targeting hepatocytes, kupffer cells, or hepatic stellate cells (HSC). Despite these promising advances, challenges including nonspecific sequestration by Kupffer cells, physical instability during storage, and limited clinical translation continue to restrict the therapeutic potential of nanocrystal‐based liver drug delivery systems. Further novel perspectives, such as artificial intelligence‐assisted preparation, liver‐on‐a‐chip technology, and Quality by Design approaches, are presented to develop NCs more comprehensively toward precision nanomedicines for treating liver fibrosis, hepatitis, or hepatic cancer.
One of the biggest causes of morbidity and mortality in the world today is sepsis, primarily due to dysregulated host responses that culminate in systemic inflammation, oxidative stress, and progressive multi-organ failure. Conventional therapeutics are limited by poor pharmacokinetics, inadequate organ-specific delivery, rapid systemic clearance, and dose-limiting toxicity. Nanotechnology offers promising solutions by improving drug stability, enhancing bioavailability, and enabling targeted and controlled delivery to affected organs. Advances in nanocarrier engineering, including liposomes, polymeric nanoparticles, lipid-based systems, inorganic nanomaterials, and hybrid platform,s have enabled modulation of immune pathways, attanuates inflammatory cascades, bacterial toxins, and scavenging of excessive reactive oxygen species implicated in sepsis progression. Furthermore, organ-targeted and stimuli-responsive nanosystems have demonstrated potential to selectively accumulate in injured kidneys, lungs, liver, spleen, and the brain, thereby improving therapeutic index and reducing off-target effects. Emerging smart nanocarriers provide spatiotemporal release in response to disease-specific microenvironmental cues such as pH, enzymes, and oxidative species. This review summarizes current progress in nano-enabled therapeutic strategies for sepsis-induced acute organ injuries, discusses targeting mechanisms and delivery platforms, and highlights translational advancements and remaining barriers toward clinical adoption. Nanotechnology-based interventions represent a transformative approach with potential to redefine treatment paradigms in sepsis and associated organ failure.
Neurodegenerative diseases (NDs) are characterized by slow progression and late detection, seriously compromising the efficiency of treatments. The presence of the blood-brain barrier (BBB) significantly impairs conventional therapies. More recently, extracellular vesicles (EVs) have emerged as promising drug delivery systems for brain-targeted therapies due to their ability to cross the BBB and their combination of low immunogenicity, high biocompatibility, and delivery efficiency. EVs play a vital role in intercellular communication, transporting nucleic acids, lipids, and proteins between cells, which are crucial for modulating cellular functions, immune responses, and neuroprotection. They have also demonstrated considerable therapeutic potential by mitigating neuroinflammation, reducing neuronal damage, and alleviating cognitive deficits in preclinical models of NDs. This review discusses various applications of EVs in the treatment of NDs, challenges they present as a delivery vehicle, and future research directions and regulatory considerations in advancing EV-based therapies for neurodegenerative disorders.
Huntington’s disease (HD) is a progressive neurodegenerative disorder caused by mitochondrial dysfunction, oxidative stress, and neuroinflammation, for which effective therapies remain undiscovered. In the present study, a piperine-loaded liposomal thermoresponsive hydrogel (PI-LP-G) was developed as a potential nose-to-brain delivery system, and its neuroprotective potential was evaluated in SHSY-5Y cells and SD rats with HD-like symptoms induced by 3-nitropropionic acid (3-NP). The ethanol injection method was used to fabricate liposomes, which were then further loaded into a thermoresponsive hydrogel. Compared to the free piperine, the oxidative stress reduction and mitochondrial repolarisation potential of liposomes were estimated using DCFH-DA and JC-1 assays. Neurobehavioral assessment was utilised to assess the neuroprotective role. Piperine liposomes (PI-LPs) were optimised to get stable nanosized vesicles (109 ± 2.1 nm) with high encapsulation efficiency (75.8 ± 1.8
Wilson's disease is a genetic disorder characterised by dysfunction of the ATP7B gene, leading to excessive copper accumulation in the body. This accumulation contributes to oxidative stress and progressive neurodegeneration, posing significant challenges for treatment. This study employed molecular docking to screen phytomolecules against ATP7B, identifying silymarin as the lead candidate based on its favourable binding affinity and interaction profile. Silymarin-loaded liposomes (SIL-LP) were optimised using a Central Composite Design, yielding a particle size of 173.4 nm, 86.05% encapsulation efficiency, and a zeta potential of −29 mV. The optimised liposomes exhibited sustained drug release (~81% in 24 h), reduced drug crystallinity, and enhanced antioxidant activity. Subsequently, the SIL-LPs were incorporated into a thermosensitive intranasal hydrogel (SIL-LP-G) that demonstrated appropriate gelation behaviour, favourable rheological properties, enhanced ex vivo nasal permeation, and good nasal mucosal compatibility. In SH-SY5Y cells, SIL-LPs showed superior cytocompatibility, significantly reduced CuSO₄-induced reactive oxygen species generation, and restored mitochondrial membrane potential compared with free silymarin. These results showed the potential of the developed platform for management of Wilson's disease.
Glioblastoma (GBM) is a prevalent and highly aggressive type of brain tumour that frequently occurs in older individuals. Radiotherapy solely offers palliative relief; however, it has been observed that chemotherapeutic drugs are only beneficial in enhancing the quality of life in GBM patients with minimal impact on the mortality rate. Moreover, only a limited drug therapy is available for the treatment of GBM, which is the primary reason for the global burden of mortality over the years. Chemotherapeutic agents primarily fail to reach the brain and the tumour site due to the presence of the blood-brain tumour barrier (BBTB)/blood-brain barrier (BBB), which prevents access to the tumour microenvironment. Moreover, other factors such as high tumour recurrence, drug resistance, and treatment costs further worsen the management of GBM. Thus, optimizing the existing drug therapy to improve its biopharmaceutical performance has been seen as an alternative approach for GBM treatment. Smart nanomedicines, including liposomes, nanomicelles, polymeric and lipidic nanoparticles, and nanocomposites, are constituted of biomimetic lipids and biocompatible polymers, which have demonstrated excellent drug loading and ability to cross the BBB and BBTB for GBM treatment. Surface modification of nanocarriers with ligands (e.g., folate, lectin, transferrin, glutamate), growth factors, functional peptides, and monoclonal antibodies has significantly improved their potential for targeting drugs and nucleic acids for GBM. Moreover, recent innovations in drug therapies, such as the incorporation of theragnostic agents into nanocarriers and antibody-drug conjugates, have provided new insights into the treatment and diagnosis of glioma. This keynote review presents recent advances in therapeutic interventions for GBM, with special emphasis on nanotherapeutic systems to achieve maximal therapeutic benefits.