Search Results (307)

Amphiphilic block copolymers are essential for developing advanced polymer nanomaterials with applications in bioimaging, drug delivery, and nanoreactors. In this study, we successfully synthesized functional block copolymer assemblies at high concentrations through redox-initiated reversible addition–fragmentation chain transfer (RAFT) emulsion polymerization of 2-(acetoacetoxy)ethyl methacrylate (AEMA), a β-ketoester functional monomer. Utilizing a redox initiation system at 50 °C, we produced poly(poly(ethylene glycol) methyl ether methacrylate)-b-PAEMA (PPEGMA_n-PAEMA_m). Kinetic studies demonstrated rapid monomer conversion exceeding 95% within 30 min, with distinct polymerization phases driven by micelle formation and monomer depletion. Transmission Electron Microscopy (TEM) and Dynamic Light Scattering (DLS) revealed the formation of diverse morphologies, including worm-like, vesicular structures, and spherical micelles, depending on the macro-CTA molecular weight and monomer concentration. Additionally, post-polymerization modification with aggregation-induced emission (AIE) luminogens, such as 1-(4-aminophenyl)-1,2,2-tristyrene (TPE-NH₂), resulted in AIE-active polymer assemblies exhibiting strong fluorescence in aqueous dispersions. These AIE-active polymer assemblies also exhibited good biocompatibility. These findings demonstrate the efficacy of redox-initiated RAFT emulsion polymerization in fabricating functional, scalable block copolymer assemblies with potential applications in the field of life sciences. Full article

The use of topical and transdermal drug delivery systems for nonsteroidal anti-inflammatory drugs (NSAIDs) has transformed pain management, inflammation, and skin conditions. This analysis highlights the topical and transdermal applications of ibuprofen, ketoprofen, and flurbiprofen, highlighting their excellent skin permeability and localized pain relief, as well as an evaluation of their safety in such applications. Their compatibility with diverse formulations, minimal systemic side effects, and widespread use in commercial products makes them ideal candidates for skin research and targeted therapy. Advances in transdermal delivery processes, such as the use of chemical enhancers, Solid Lipid Nanoparticles, vesicular systems, and hydrogels, have enhanced NSAID penetration and bioavailability. Physical techniques like iontophoresis and sonophoresis further enhance the transport of drugs across the stratum corneum of the skin. These approaches and processes enable more efficient and localized treatment of inflammatory conditions. The review emphasizes the need for continued innovation, interdisciplinary processes, and collaboration to overcome existing challenges. Future developments in nanotechnology and advanced drug delivery systems have the capability to enhance the effectiveness and safety of NSAIDs, paving the way for novel therapeutic solutions in managing pain and inflammation. Full article

In this study, vesicular lipid systems and semi-solid formulations for the skin application of Palmitoyl-GHK were formulated and characterized. Palmitoyl-GHK is a cosmetic peptide with anti-aging action, capable of treating the signs of skin aging by mainly stimulating collagen synthesis in the dermis. The so-called “ethosomes” were evaluated as nanovesicular systems constituted of phosphatidylcholine, organized in vesicles, ethanol, and water. In addition, semi-solid systems were produced and characterized, namely an organogel based on phosphatidylcholine, isopropyl palmitate, and water, a gel based on Poloxamer 407, and the poloxamer organogel, created by combining organogel and Poloxamer gel. To make the ethosomal dispersions suitable for skin application, xanthan gum was added as a gelling agent. Studies were therefore carried out on semi-solid formulations to determine (i) the spreadability, a key factor that influences various aspects of a topical/transdermal formulation, (ii) the occlusive factor, important to guarantee good effectiveness of a dermocosmetic product, and finally, (iii) the hydrating power, to study the effect of a formulation applied to the skin. A formulation study enabled the selection of the most suitable formulations for the incorporation of the active ingredient of interest. Palmitoyl-GHK was found to be soluble both in ethosomes and in the poloxamer organogel. In vitro studies were therefore conducted to evaluate the release kinetics of Palmitoyl-GHK from the formulations, via Franz cells. The qualitative–quantitative analysis, through analytical HPLC, highlighted that the active ingredient is released more slowly from semi-solid formulations compared to vesicular systems; in particular, the presence of poloxamer allows a controlled release of the peptide. Further studies will be necessary to verify the anti-aging efficacy of formulations containing the peptide. Full article

Cosmeceuticals are cosmetic products containing biologically active ingredients claiming to have drug-like benefits. In recent years, there has been a growing global demand for cosmeceuticals focusing on visible improvement of skin appearance and health. However, modern consumers are increasingly more concerned about the performance and clinical efficacy of cosmetic formulations. One of the main disadvantages of cosmeceutical preparations is the poor transdermal delivery of active ingredients included in the formulation. In response to this challenge, many phospholipid-based nanovesicular delivery systems have been developed and tested in recent years to increase the skin penetration of active cosmetic molecules. This review provides a comprehensive overview of current knowledge in the research and development of liposomal encapsulation used as delivery system in skincare and cosmeceutical products. Full article

Niosomes are a stable vesicular system composed of non-ionic surfactants and cholesterol, offering advantages such as enhanced stability and controlled drug release. In this study, a niosomal nanogel loaded with Ebastine was developed to improve patient compliance in treating skin allergic reactions. Thin-film hydration was employed to prepare niosomes using cholesterol, Span 60, Tween 80, and Ebastine, optimized via Box–Behnken experimental design. A dispersion method incorporating Carbopol 934 was utilized to create a niosomal gel, ensuring effective therapeutic outcomes. The formulation exhibited high drug entrapment efficiency (84.19%), a zeta potential of −27 mV, and vesicle sizes ranging from 100 to 300 nm. Evaluation included FTIR for drug–excipient compatibility, pH assessment, in vitro drug release studies, and stability testing, all yielding acceptable results. The encapsulation of Ebastine within niosomes is driven by critical physicochemical interactions between the drug, cholesterol, and surfactants. These interactions influence the stability, encapsulation efficiency, and release profile of the drug from the niosomal bilayer. Microbial studies indicated significant antimicrobial activity against S. aureus, underscoring its potential as an effective transdermal treatment for skin allergies. Full article

Nano-drug delivery systems provide targeted solutions for addressing various drug delivery challenges, leveraging nanotechnology to enhance drug solubility and permeability. Liposomes, explored for several decades, face hurdles, especially in oral delivery. Bile-acid stabilized vesicles (bilosomes) are flexible lipid vesicles, composed of phospholipids or other surfactants, along with amphiphilic bile salts, and they show superior stability and pharmacokinetic behavior in comparison to conventional vesicular systems (liposomes and niosomes). Bilosomes enhance skin penetration, fluidize the stratum corneum, and improve drug stability. In oral applications, bilosomes overcome drawbacks, offering improved bioavailability, controlled release, and reduced side effects. Vaccines using bilosomes demonstrate efficacy, and bilosomes for intranasal, inhalation, ocular, and buccal applications enhance drug delivery, offering targeted, efficient, and controlled activities. Formulations vary based on active substances and optimization techniques, showcasing the versatility and potential of bilosomes across diverse drug delivery routes. Therefore, the aim of this comprehensive review was to critically explore the state-of-the-art of bilosomes in drug delivery and potential therapeutic applications. Full article

The blood–brain barrier (BBB) comprises distinct cell types, including endothelial cells, pericytes, and astrocytes, and is essential for central nervous system (CNS) homeostasis by selectively regulating molecular transport and maintaining integrity. In particular, astrocytes are essential for BBB function, as they maintain BBB integrity through their end-feet, which form a physical and biochemical interface that enhances endothelial cell function and barrier selectivity. Moreover, they secrete growth factors like vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-β), which regulate tight junction (TJ) proteins (e.g., claudins and occludins) crucial for limiting paracellular permeability. Molecular motors like kinesins, dynein, and myosins are essential for these astrocyte functions. By facilitating vesicular trafficking and protein transport, they are essential for various functions, including trafficking of junctional proteins to support BBB integrity, the proper mitochondria localization within astrocyte processes for efficient energy supply, the polarized distribution of aquaporin (AQP)-4 at astrocyte end-feet for regulating water homeostasis across the BBB, and the modulation of neuroinflammatory responses. Moreover, myosin motors modulate actomyosin dynamics to regulate astrocyte process outgrowth, adhesion, migration, and morphology, facilitating their functional roles. Thus, motor protein dysregulation in astrocytes can compromise BBB function and integrity, increasing the risk of neurodegeneration. This review explores the complex interplay between astrocytes and molecular motors in regulating BBB homeostasis, which represents an attractive but poorly explored area of research. Full article

In an era of significant developments in cosmetic chemistry and growing demand for efficacious skincare products, the efficient delivery of active molecules has been a challenge in formulations of cosmetics. In order to improve the performance of active compounds, the use of different nanotechnology-based systems have been explored in cosmetic chemistry. Niosomes, self-assembled vesicular nanocarriers, have been used in the cosmetic industry since the 1970s. The aim of this review is to provide a comprehensive overview of recent advancements in the encapsulation of active cosmetic compounds using niosomes as potential carriers for their sustained and targeted delivery. The review discusses the physicochemical, pharmacokinetic and pharmacodynamic properties of niosomes, including preparation methods, advantages and limitations. Various applications of niosomes in the cosmetic industry are presented together with the permeation and efficacy data from conducted in vitro and in vivo studies. Future perspectives of these nanocarriers for cosmetic applications are highlighted. Full article

As the mechanisms underlying tumorigenesis become better understood, the dynamic roles of cellular components of the tumor microenvironment, and their cross-talk with tumor cells, have come to light as key drivers of disease progression and have emerged as important targets of new cancer therapies. In the field of oncolytic virus (OV) therapy, stromal cells have been considered as potential barriers to viral spread, thus limiting virus replication and therapeutic outcome. However, new evidence indicates that intratumoral fibroblasts could support virus replication. We have demonstrated in a rat model of stromal-rich intrahepatic cholangiocarcinoma (CCA) that vesicular stomatitis virus (VSV) can be localized within intratumoral hepatic stellate cells (HSCs), in addition to tumor cells, when the virus was applied via hepatic arterial infusion. Furthermore, VSV was shown to efficiently kill CCA cells and activated HSCs, and co-culture of CCA and HSCs increased viral titers. Interestingly, this effect is also observed when each cell type is cultured alone in a conditioned medium of the other cell type, indicating that secreted cell factors are at least partially responsible for this phenomenon. Partial reduction in sensitivity to type I interferons was observed in co-culture systems, providing a possible mechanism for the increased viral titers. Together, the results indicate that targeting activated HSCs with VSV could provide an additional mechanism of OV therapy, which, until now has not been considered. Furthermore, these findings suggest that VSV is a potentially powerful therapeutic agent for stromal-rich tumors, such as CCA and pancreatic cancer, both of which are very difficult to treat with conventional therapy and have a very poor prognosis. Full article

The current opinion manuscript posits that not only Piezo2 voltage block, but also proton affinity and availability in relation to Piezo2, a mechanically gated ion channel, may count in the mediation of pain and its sensitivity. Moreover, this paper argues that autonomously acquired Piezo2 channelopathy on somatosensory terminals is likely the initiating peripheral impaired input source that drives the central sensitization of spinal nociceptive neurons on the chronic path as being the autonomous pain generator. In parallel, impaired proprioception and the resultant progressive deficit in neuromuscular junctions of motoneurons might be initiated on the chronic path by the impairment of the proton-based ultrafast proprioceptive feedback to motoneurons due to disconnection through vesicular glutamate transporter 1. The irreversible form of this autonomously acquired Piezo2 ion channel microdamage, in association with genetic predisposition and/or environmental risk factors, is suggested to lead to progressive motoneuron death in addition to loss of pain sensation in amyotrophic lateral sclerosis. Furthermore, the impairment of the proton-based ultrafast long-range oscillatory synchronization to the hippocampus through vesicular glutamate transporter 2 may gain further importance in pain modulation and formation on the chronic path. Overall, this novel, unaccounted Piezo2-initiated protonic extrafast signaling, including both the protonic ultrafast proprioceptive and the rapid nociceptive ones, within the nervous system seems to be essential in order to maintain life. Hence, its microdamage promotes neurodegeneration and accelerates aging, while the complete loss of it is incompatible with life sustainment, as is proposed in amyotrophic lateral sclerosis. Full article

In a recent clinical trial, beetroot juice supplementation for 14 days yielded positive effects on systemic inflammation in adults with long COVID. Here, we explored the relationship between circulating markers of mitochondrial quality and inflammation in adults with long COVID as well as the impact of beetroot administration on those markers. We conducted secondary analyses of a placebo-controlled randomized clinical trial testing beetroot juice supplementation as a remedy against long COVID. Analyses were conducted in 25 participants, 10 assigned to placebo (mean age: 40.2 ± 11.5 years, 60% women) and 15 allocated to beetroot juice (mean age: 38.3 ± 7.7 years, 53.3% women). Extracellular vesicles were purified from serum by ultracentrifugation and assayed for components of the electron transport chain and mitochondrial DNA (mtDNA) by Western blot and droplet digital polymerase chain reaction (ddPCR), respectively. Inflammatory markers and circulating cell-free mtDNA were quantified in serum through a multiplex immunoassay and ddPCR, respectively. Beetroot juice administration for 14 days decreased serum levels of interleukin (IL)-1β, IL-8, and tumor necrosis factor alpha, with no effects on circulating markers of mitochondrial quality control. Significant negative associations were observed between vesicular markers of mitochondrial quality control and the performance on the 6 min walk test and flow-mediated dilation irrespective of group allocation. These findings suggest that an amelioration of mitochondrial quality, possibly mediated by mitochondria-derived vesicle recycling, may be among the mechanisms supporting improvements in physical performance and endothelial function during the resolution of long COVID. Full article

The ubiquitin proteasome system (UPS) is implicated in protein homeostasis. One of the proteins involved in this system is HERC1 E3 ubiquitin ligase, which was associated with several processes including the normal development and neurotransmission at the neuromuscular junction (NMJ), autophagy in projection neurons, myelination of the peripheral nervous system, among others. The tambaleante (tbl) mouse model carries the spontaneous mutation Gly483Glu substitution in the HERC1 E3 protein. Using this model, we analyzed the implication of HERC1 E3 ubiquitin ligase in the activity of UPS, autophagy, and synaptic homeostasis in brain and muscle tissues. Regarding UPS, no differences were found in its activity nor in the specific gene expression in both brain and muscle tissues from tbl compared with the control littermates. Furthermore, the use of the specific UPS inhibitor (MG-132), did not alter the evoked neurotransmitter release in the levator auris longus (LAL) muscle. Interestingly, the expression of the autophagy-related gene p62 was significantly increased in the muscle of tbl compared to the control littermates. Indeed, impaired evoked neurotransmitter release was observed with the autophagy inhibitor Wortmannin. Finally, altered levels of Clathrin and Synaptophysin were detected in muscle tissues. Altogether, our findings show that HERC1 E3 ubiquitin ligase mutation found in tbl mice alters autophagy and vesicular recycling without affecting proteasomal function. Full article

In the 21st century, thanks to advances in biotechnology and developing pharmaceutical technology, significant progress is being made in effective drug design. Drug targeting aims to ensure that the drug acts only in the pathological area; it is defined as the ability to accumulate selectively and quantitatively in the target tissue or organ, regardless of the chemical structure of the active drug substance and the method of administration. With drug targeting, conventional, biotechnological and gene-derived drugs target the body’s organs, tissues, and cells that can be selectively transported to specific regions. These systems serve as drug carriers and regulate the timing of release. Despite having many advantageous features, these systems have limitations in thoroughly treating complex diseases such as cancer. Therefore, combining these systems with nanoparticle technologies is imperative to treat cancer at both local and systemic levels effectively. The nanocarrier-based drug delivery method involves encapsulating target-specific drug molecules into polymeric or vesicular systems. Various drug delivery systems (DDS) were investigated and discussed in this review article. The first part discussed active and passive delivery systems, hydrogels, thermoplastics, microdevices and transdermal-based drug delivery systems. The second part discussed drug carrier systems in nanobiotechnology (carbon nanotubes, nanoparticles, coated, pegylated, solid lipid nanoparticles and smart polymeric nanogels). In the third part, drug targeting advantages were discussed, and finally, market research of commercial drugs used in cancer nanotechnological approaches was included. Full article

Background/Objectives: Spironolactone (SP), an aldosterone inhibitor widely used to treat androgen-dependent disorders such as acne, hirsutism, and alopecia, has demonstrated therapeutic potential in both oral and topical formulations. However, SP’s low solubility and poor bioavailability in conventional formulations have driven the development of novel nanocarriers to enhance its efficacy. This review systematically examines recent advancements in SP-loaded nanocarriers, including lipid nanoparticles (LNPs), vesicular nanoparticles (VNPs), polymeric nanoparticles (PNPs), and nanofibers (NFs). Methods: A search strategy was developed, and the relevant literature was systematically searched using databases such as Scopus, PubMed, and Google Scholar. The review process, including screening, inclusion, and exclusion criteria, adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: A comprehensive analysis of 13 eligible research articles, corresponding to 15 studies, highlights key aspects such as encapsulation efficiency, stability, particle size, and in vitro and in vivo efficacy. Six studies focused on lipid nanoparticles (LNPs), including solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), which were found to improve SP’s bioavailability and skin permeation. Another six studies investigated vesicular nanoparticles (VNPs), such as ethosomes and niosomes, demonstrating superior skin targeting and penetration capabilities. Two studies on polymeric nanoparticles (PNPs) showed effectiveness in delivering SP to hair follicles for the treatment of alopecia and acne. Additionally, one study on SP-loaded nanofibers indicated significant potential for topical rosacea therapy. Conclusions: SP-loaded nanocarrier systems represent promising advancements in targeted topical therapy. However, further clinical studies are required to optimize their safety, efficacy, and delivery mechanisms. Full article

Background/Objectives: Ovarian cancer is the deadliest gynecologic cancer, and with the majority of patients dying within the first five years of diagnosis, new therapeutic options are required. The small guanosine triphosphatase (GTPase) Ras-related nuclear protein (Ran) has been reported to be highly expressed in high-grade serous ovarian cancers (HGSOCs) and associated with poor outcomes. Blocking Ran function or preventing its expression were shown to be promising treatment strategies, however, there are currently no small molecule inhibitors available to specifically inhibit Ran function. Interestingly, a previous study suggested that the Vesicular stomatitis virus (VSV) could inhibit Ran activity. Given that VSV is an oncolytic virus (OV) and, therefore, has anti-cancer activity, we reasoned that oncolytic VSV (oVSV) might be particularly effective against ovarian cancer via Ran inhibition. Methods: We evaluated the sensitivity of patient-derived ovarian cancer cell lines to oVSV, as well as the impact of oVSV on Ran and vice versa, using overexpression systems, small interfering RNAs (siRNAs), and drug inhibition. Results: In this study, we evaluated the interplay between oVSV and Ran and found that, although oVSV does not consistently block Ran, increased Ran activation allows for better oVSV replication and tumor cell killing. Conclusions: Our study reveals a positive impact of Ran on oVSV sensitivity. Given the high expression of Ran in HGSOCs, which are particularly aggressive ovarian cancers, our data suggest that oVSV could be effective against the deadliest form of the disease. Full article