Search Results (493)

During aging, skeletal muscle undergoes a decline in mass and strength. This condition, known as sarcopenia, involves many physiological and metabolic impairments, thus representing a healthcare, social, and economic burden. Various pharmacological and non-pharmacological approaches have been explored to counteract sarcopenia; however, no definite treatment has so far been found. The present narrative review summarizes nanotechnology-based strategies designed to promote muscle preservation and functional recovery in aging. Synthetic organic or inorganic nanoconstructs and natural extracellular vesicles have been used as nanocarriers for drug delivery, have been active as intrinsic therapeutic agents, have been employed to build biomimetic nanoscaffolds to sustain muscle regeneration, or have been combined to form hybrid nanosystems with multiple therapeutic functions. These nanotools demonstrated promising results in vitro and in animal models, being able to counteract major factors responsible for sarcopenia, such as oxidative stress, inflammation, mitochondrial dysfunction, increased proteolysis, and impaired stem cell function. However, nanotools have mostly been tested on biological models far from the physiologically aged human muscle. Moreover, limitations still remain to be solved to make these nanotools suitable for regenerative medicine; in particular, the systemic administration requires nanoconstruct functionalization for skeletal muscle targeting, and proper clearance should be ensured to avoid toxicity and immunogenicity related to long-term use. Full article

Breast cancer remains one of the leading causes of cancer-related mortality among women worldwide, highlighting the need for safer and more effective chemopreventive strategies. Although many phytochemicals can modulate key molecular processes involved in breast carcinogenesis, their chemopreventive potential largely depends on delivery strategies that preserve their biological activity and enable efficient accumulation at the target site. Protein-based nanocarriers have emerged as promising delivery systems capable of improving the protection, solubility, cellular uptake, targeted delivery, and controlled release of bioactive compounds in tumor tissues. This review summarizes recent advances in selected animal- and plant-derived protein nanocarriers used for the encapsulation and delivery of natural compounds in breast cancer chemoprevention. Particular attention is given to their physicochemical properties, encapsulation performance, release behavior, biological activity, targeting potential, and translational limitations. Furthermore, the mechanisms underlying the enhanced anticancer activity of encapsulated phytochemicals, including improved stability, receptor-mediated uptake, pH-responsive release, apoptosis induction, oxidative stress modulation, and inhibition of tumor growth and metastasis, are highlighted. Current challenges, including enzymatic degradation, formulation instability, immunogenicity concerns, manufacturing scalability, and limited clinical evidence, remain important barriers to translation. Overall, selected protein-based nanocarriers represent promising multifunctional platforms for improving the chemopreventive potential of natural compounds in breast cancer. Full article

Diabetes mellitus (DM) is a highly prevalent metabolic disorder and a major public health concern. Pioglitazone, a widely used antidiabetic agent, exhibits limited therapeutic efficiency due to poor water solubility and suboptimal pharmacokinetic properties. Similarly, curcumin (Cur), a natural polyphenol with pleiotropic biological activities, is hindered by low oral bioavailability. In this study, chitosan-based nanocarriers were developed for the delivery of pioglitazone (CS-Pio NPs), curcumin (CS-Cur NPs), and their co-encapsulation (CS-Pio-Cur NPs), aiming to enhance their biological performance and therapeutic efficacy. The co-loaded nanosystem (CS-Pio-Cur NPs) demonstrated significantly enhanced antioxidant activity, as evidenced by DPPH (71.29 ± 0.09%), ABTS (86.08 ± 0.04%), and hydroxyl radical scavenging (87.08 ± 0.06%) assays, along with a strong reducing capacity (IC₅₀ = 25.39 ± 0.23 μg/mL). In a diabetic rat model, CS-Pio-Cur NPs significantly reduced blood glucose level and HbA1c (6.60 ± 0.83%), while also improving liver and kidney function parameters and lipid profile. These findings suggest that co-delivery of Pio and Cur via CS-based nanocarriers provides a combined therapeutic effect by simultaneously targeting hyperglycemia, oxidative stress, and associated metabolic dysfunctions. This nanosystem represents a promising approach for improving the management of DM and its complications. Full article

Several sensitive bioactive substances are potent antioxidants that protect the skin from free radicals but are often rapidly degraded, limiting their effectiveness. Encapsulating these substances in liposomes improves their bioavailability and solubility and protects them from harmful environmental factors. The influence of liposomes as advanced lipid nanocarriers is increasing enormously due to their remarkable properties and protection of bioactive substances. For this reason, mango (Mangifera indica L.) peel extract (MPE), previously characterized and rich in various natural substances, including ellagic acid, gallic acid, and catechin, has been encapsulated in liposomes. The investigation focused on the impact of different liposome synthesis process parameters on their size, size distribution, stability, and encapsulation efficiency, and on in vitro release as a potential advanced MPE delivery system with suitable characteristics. An important study on the influence of the organic solvent used in liposome synthesis on the above properties is described. The thin lipid film hydration method using 5-mm glass beads and ethanol as an organic solvent was the most favorable method for synthesizing a stable and monodisperse lipid–MPE delivery system. MPE was successfully encapsulated in liposomes with the highest encapsulation efficiency of 53.7%. The sustained release of MPE from the liposomes was achieved, and the antibacterial properties of MPE, incorporated into the liposomes, were retained. For the first time, MPE has been encapsulated in liposomes, and with the remarkable results obtained, the extract represents a formulation with high added value that can be used in various fields, especially for the enrichment of different products such as cosmetic creams and lotion. Full article

Sulforaphane (SFN), a bioactive compound sourced from cruciferous vegetables, offers significant antioxidant and anti-inflammatory benefits yet its stability in animal feed is a challenge. Nanotechnology-based encapsulation, specifically ionic gelation, has demonstrated efficacy in improving the stability and bioavailability of SFN. This review examines the application of natural polymers such as chitosan and alginate in ionic gelation for the encapsulation of SFN. It also discusses how these polymers can prevent SFN from degrading while traversing the digestive tract. Encapsulation strategies for SFN have been associated with improved bioavailability, with absorption reported in experimental modules, to modulate immune-related and oxidative-stress pathways. However, challenges persist in identifying optimal methods for encapsulating various species, including enhancing encapsulation effectiveness, particle size, and controlled release mechanisms. Additionally, regulatory concerns regarding the safety and environmental impacts of nanoparticles in feed must be addressed. Future research should focus on improving encapsulation techniques and ensuring the safe application of SFN-loaded nanocarriers in livestock feed. Full article

Extracellular vesicles (EVs) and liposomes are nanoscale drug delivery systems extensively investigated in oncology for their ability to improve pharmacokinetics, biodistribution, and therapeutic efficacy of anticancer agents. Liposomes are clinically validated synthetic nanocarriers characterized by high versatility, scalable production, and established regulatory approval; however, their performance is limited by tumor heterogeneity, vascular barriers, adverse effects and inefficient intracellular drug release. EVs are naturally derived nanoparticles involved in intercellular communication and exhibit intrinsic biocompatibility, low immunogenicity, and biological targeting potential; yet their translation is constrained by heterogeneity, limited loading capacity, and manufacturing challenges. Different studies indicate complementary advantages between both systems, with EVs favoring biological targeting and immune modulation and liposomes enabling controlled formulation and pharmacokinetic optimization. These features have driven the development of hybrid EV–liposome nanovesicles, which integrate synthetic and biological properties to enhance tumor targeting, therapeutic efficacy, and payload diversity, including drugs, nucleic acids, and gene-editing systems. Despite promising preclinical results, challenges remain in scalability, standardization, and mechanistic understanding of in vivo behaviour. Overall, these hybrid strategies represent a promising platform for next-generation precision nanomedicine in cancer therapy and for advancing clinical translation by addressing key limitations of current delivery systems and improving therapeutic index and patient outcomes. Full article

Daidzein is a naturally occurring isoflavone phytoestrogen, mainly found in leguminous plants. This component exerts anti-inflammatory effects by regulating inflammatory cells via multiple targets, blocking core inflammatory pathways, and inhibiting the release of inflammatory factors. It also scavenges reactive oxygen species, activates the antioxidant enzyme system, and regulates antioxidant signaling pathways to achieve antioxidant effects. By regulating these two core pathological processes, it exerts protective effects in diseases such as cancer, cardiovascular disease, and acute kidney injury, based on preclinical evidence. The development of nanodelivery systems has effectively improved the physicochemical properties of daidzein, enhanced its bioavailability, and enabled disease-targeted delivery. Most previous reviews have either focused exclusively on daidzein or broadly covered the pharmacological activities of isoflavones, yet have largely overlooked the dual anti-inflammatory and antioxidant mechanisms specific to daidzein. This review summarizes these mechanisms and their preclinical effects on various diseases, including cancer, cardiovascular diseases, and acute kidney injury. It also reviews the pharmacokinetic limitations of daidzein and recent progress in nanodelivery strategies aimed at enhancing its bioavailability and bioactivity. Overall, this review serves as a reference for the future standardized comparison of nanocarriers, targeted therapies, and clinical applications. Full article

Background/Objective: Topical therapy remains a cornerstone in managing fungal infections due to the deep-seated nature of the pathogens and the persistence of the disease. Ketoconazole (KTZ) is a broad-spectrum antifungal agent, but its highly lipophilic nature presents considerable challenges in developing effective topical formulations. Additionally, oral KTZ has been subject to labeling restrictions and market withdrawal due to its association with severe hepatic adverse effects. This study was conducted to design, optimize, and evaluate KTZ-loaded nanolipid carriers (NLCs; KTZ-NLCs) as a delivery platform that could improve cutaneous bioavailability and enhance antifungal activity. Methods: The optimized KTZ-NLCs were further incorporated into a mucoadhesive system (KTZ-NLCs-C) through the inclusion of Carbopol^® 940 NF, aiming to improve the retention of the formulation on the skin surface. NLCs were characterized in terms of their physical appearance, particle size, polydispersity index, zeta potential, pH, viscosity, drug content, and entrapment efficiency. The optimized KTZ-NLC and KTZ-NLCs-C formulations were subsequently assessed for in vitro drug release, ex vivo skin permeation and deposition, as well as in vivo skin irritation. Results: In vitro release studies revealed that nanocarrier systems provided a sustained release of KTZ over 24 h. The ex vivo transdermal flux and permeability coefficient of KTZ from the lead KTZ-NLCs-C formulation were approximately 2.8-fold greater than those achieved with the marketed cream formulation. The in vivo skin irritation studies indicate that NLC-based formulations are suitable for topical applications. The lead formulation was stable for 90 days (the final time point evaluated) under refrigerated and room-temperature storage conditions. Conclusions: These findings suggest that the NLC-based system is a promising platform for the topical delivery of KTZ and has the potential to enhance the therapeutic outcomes for patients with superficial fungal infections. Full article

Fish are continuously exposed to stress factors throughout their life cycle, making the use of anaesthetics essential for a wide range of experimental procedures. Currently, the most commonly used and FDA approved anaesthetic for fish research is Tricaine Methanesulfonate (MS-222). However, its use has been associated with several undesirable effects, including hypoxemia, hypercapnia and hypoglycaemia, as well as environmental concerns due to its release through aquaculture effluents. These limitations highlight the need for alternative anaesthetic strategies. Natural compounds such as clove oil, menthol and thymol have been investigated as potential alternatives, demonstrating effective anaesthetic properties. However, their low aqueous solubility, represents a significant challenge, which may be overcome through nanoencapsulation. This approach can enhance solubility, enable controlled release, and reduce the effective dose required. Accordingly, the present study aims to provide an overview of the recent advances in nanoparticle-based encapsulation strategies for anaesthetic delivery in fish, with a focus on their efficacy, safety and environmental impact. Some studies have demonstrated the benefits of nanoencapsulation. In adult zebrafish (Danio rerio), lower concentrations of benzocaine were required when encapsulated in chitosan-PLGA nanoparticles, while lidocaine-loaded lipid NPs reduced bradycardia. In Nile Tilapia (Oreochromis niloticus), clove oil encapsulated in lipid-based nanocapsules enabled effective anaesthesia and prolonged release of the active compound eugenol. Similarly, mucoadhesive zein NPs, reduced the effective concentration of Eugenol by up to 50%. Monoterpenes such as menthol and thymol also show promise for zebrafish anaesthesia, demonstrating efficacy at 50 mg/L. These findings suggest that nanoparticle-based delivery systems can improve the efficacy and safety of fish anaesthetics while reducing required doses and potential environmental impact. Future research should focus on optimizing nanoparticle-anaesthetic systems by combining natural compounds with biocompatible and biodegradable nanocarriers (e.g., zein, chitosan or PLGA) to achieve controlled release, targeted delivery and minimization of side effects. Full article

Cancer progression is closely associated with dysregulation of apoptosis, enabling malignant cells to evade programmed cell death and develop resistance to therapy. Among the key regulators of this process, the tumor suppressor protein p53 and the Bcl-2 family of proteins play central and interconnected roles in controlling cell survival and mitochondrial integrity. In recent years, naturally occurring flavonoids have attracted considerable attention as potential modulators of these pathways due to their diverse biological activities and relatively low toxicity. This review provides a focused and integrative overview of how different subclasses of flavonoids modulate the p53–Bcl-2 signaling axis to regulate apoptosis in cancer cells. Particular emphasis is placed on the mechanistic interplay between p53 stabilization, transcriptional regulation of apoptotic targets, mitochondrial outer membrane permeabilization, and caspase activation. In contrast to previous general reviews on flavonoids and cancer, this work provides an integrated overview of evidence across multiple flavonoid subclasses and experimental cancer models, highlighting both shared and pathway-specific apoptotic responses. Experimental findings from in vitro and in vivo studies are discussed, including the effects of quercetin, kaempferol, myricetin, epigallocatechin gallate, and related compounds on cell-cycle arrest, oxidative stress, mitochondrial dysfunction, and intrinsic apoptotic signaling. Furthermore, the review examines the relationship between flavonoid chemical structure and biological activity, with particular attention to bioavailability, metabolic transformation, and strategies aimed at improving therapeutic efficacy, including structural modification and nanocarrier-based delivery systems. Despite promising preclinical findings, significant translational challenges remain, including poor pharmacokinetic properties, variability among experimental models, and limited clinical validation. Overall, flavonoids represent a promising class of bioactive compounds capable of targeting apoptosis through modulation of the p53–Bcl-2 network, and a deeper mechanistic understanding of their activity may support the development of novel targeted and combination anticancer therapies. Full article

The magnitude and quality of adaptive immune responses are fundamentally influenced by the efficiency of antigen presentation. Traditional vaccine platforms, such as live–attenuated or inactivated pathogens, although immunogenic, often present safety concerns. Conversely, subunit vaccines, despite being safer, generally exhibit poor immunogenicity due to inadequate delivery of antigens to professional antigen–presenting cells (APCs). To address this issue, the development of innovative delivery systems has become a pivotal strategy to overcome significant biological barriers, including extracellular antigen degradation, suboptimal lymph node targeting, and inefficient cross–presentation necessary for CD8+ T cell activation. This review systematically explores recent advancements in delivery technologies aimed at enhancing antigen presentation, encompassing rationally engineered nanocarriers and sophisticated biomimetic platforms. We first examine how nanoparticle properties like size, surface charge, and ligand density affect intracellular trafficking and the transition from MHC–II to MHC–I cross–presentation. Then, we explore bioinspired systems such as extracellular vesicles, virus–like particles, and cell–membrane–coated nanoparticles that utilize natural biological traits for enhanced targeting and immune modulation. Additionally, we review new physical delivery methods like microneedle arrays and in situ electroporation for direct, minimally invasive antigen delivery to dendritic cells. Lastly, we discuss the potential of these platforms in personalized cancer vaccines and combination immunotherapies. By combining insights from materials science, immunology, and bioengineering, these next–generation delivery tools could enhance antigen presentation and transform precision vaccination and immune intervention. Full article

The potential for the use of antimicrobial peptides (AMPs) as anticancer agents has garnered much interest because of their selective cytotoxicity to tumor cells and ability to evade multidrug resistance mechanisms. AMPs are shorter cationic amphiphilic molecules, part of our innate immune system, with direct membrane-disruptive activity and immunomodulatory effects. Anticancer peptides (ACPs) can be derived from natural biophysical sources or synthetically engineered, taking advantage of the unique biophysical properties of cancer cell membranes to exert their anti-tumor activities rapidly and often without significant effects on normal tissues. Advances in peptide engineering, such as D-amino acid substitution, cyclization, and PEGylation, combined with nanocarrier systems, have provided opportunities to improve peptide stability, bioavailability, and delivery to targeted sites. Studies in preclinical and clinical models show promise, indicating that AMPs and ACPs can induce immunogenic cell death, modify tumor microenvironments, and be used in combination with more conventional therapies. While the promise of AMPs and ACPs as relatively novel cancer therapeutics is substantial, challenges such as proteolytic degradation, dose-dependent toxicity, costs for production, and regulatory hurdles are notable. This review organizes the current literature on classification, mechanism(s) of action, delivery strategies, preclinical and clinical data, and provides areas for future work to improve and help speed their clinical translation as new cancer therapies. Full article

Extracellular vesicles (EVs) have attracted considerable attention as natural nanocarriers for immune modulation owing to their intrinsic biocompatibility, nanoscale size, and capacity to transport diverse bioactive cargos. In inflammatory diseases, EV-based therapeutics provide unique opportunities to regulate dysregulated immune responses; however, their clinical translation remains constrained by limited cell-specific targeting efficiency and uncontrolled biodistribution. Achieving precise and selective delivery to immune cells and other inflammation-associated cellular components within diseased tissues is therefore critical for maximizing therapeutic efficacy while minimizing off-target effects. This review comprehensively summarizes recent advances in cell-specific EV-targeting strategies for immune modulation in inflammatory diseases, with a particular focus on active targeting approaches enabled by EV surface engineering. A range of targeting ligands, including antibodies, peptides, aptamers, glycans, and membrane proteins, is discussed in the context of enhancing selective interactions between EVs and specific immune cell subsets. Special emphasis is placed on cell-directed targeting strategies toward diverse immune cell populations, including macrophages and T cells, highlighting how rational control of EV–cell interactions can be utilized to reprogram immune phenotypes, suppress pathological inflammation, and restore immune homeostasis. Accordingly, this review integrates recent progress in cell-specific EV targeting into a coherent conceptual framework, which may assist researchers in the rational design of EV-based immunomodulatory therapeutics. Full article

As a naturally self-assembling protein nanocarrier, ferritin enables multivalent antigen display and functions as an intrinsic adjuvant to enhance vaccine-induced immune responses. Streptococcus equi subsp. equi (S. equi) is the causative agent of equine strangles, an acute and highly contagious respiratory disease responsible for substantial economic losses worldwide. However, currently available vaccines often show suboptimal immunogenicity and limited protective efficacy. In this study, we developed a recombinant equine ferritin (rHF)-based nanoparticle vaccine, rSE5Mix, presenting five core protective antigens (EQ8, EQ5, CNE, IdeE, EAG). The fusion proteins efficiently assembled into uniform nanoparticles. Immunization of BALB/c mice elicited rapid, high-titer antigen-specific IgG antibodies and a balanced Th1/Th2 immune response without additional adjuvants. Following lethal challenge with S. equi, rSE5Mix-immunized mice showed 100% survival and markedly milder clinical signs. Histopathological analysis demonstrated significantly alleviated organ damage, and bacterial loads in major tissues were reduced to nearly undetectable levels. Importantly, compared with the octavalent tandem vaccine rSE8, rSE5Mix induced faster elevation of partial antigen-specific antibodies, especially for EQ8 and CNE. Their antibody titers were comparable at later stages. This study developed a safe and effective ferritin nanoparticle vaccine candidate against equine strangles and verified that equine ferritin is a promising candidate delivery platform for veterinary bacterial vaccines. Full article

Pulmonary fibrosis (PF) is a progressive and often fatal interstitial lung disease for which the currently available pharmacological therapies remain largely limited to slowing disease progression rather than reversing established fibrosis. This limitation has stimulated increasing interest in innovative therapeutic platforms capable of modulating complex fibrotic pathways. In this context, exosomes—nanoscale extracellular vesicles—have emerged as promising cell-free nanocarriers due to their intrinsic biocompatibility, low immunogenicity, and ability to be engineered for targeted drug delivery. In this review, we provide a comprehensive overview of both natural and engineered exosome-based strategies for the diagnosis and treatment of pulmonary fibrosis. We summarize recent advances in exosome engineering, including ligand functionalization, glycoengineering, and therapeutic cargo loading, highlighting how these approaches may support the development of more targeted and potentially personalized nanotherapeutic strategies. We further discuss emerging hybrid delivery platforms, such as exosome–liposome chimeras and hydrogel-based depots, which may enhance pulmonary retention, improve therapeutic durability, and enable controlled drug release. Finally, we outline key challenges and opportunities for clinical translation, including large-scale manufacturing, regulatory considerations, and clinically relevant delivery routes such as inhalation-based administration. Collectively, this review provides a translational perspective on engineered exosomes as emerging nanotherapeutic platforms for pulmonary fibrosis. Full article