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Background: The stromal vascular fraction (SVF) has been validated for enhancing tissue regeneration because of its concentration of multipotent cells and growth factors, and for mitigating inflammatory response due to its elimination of the majority of lipid droplets. However, it is difficult for fresh SVF to maintain bioactivity for a long period, and the loss of numerous tangible masses during preparation limits its application in repairing large volume defects. Here, we fabricated a self-assembly nanovesicle extruded from SVF (SVF-EVs) by mechanical shear and co-transplanted it with dermal microparticles to verify its potential for repairing large volume defects. Methods: The SVF-EVs were prepared by removing the oil from adipose tissue followed by sequentially extruding SVF through membrane filters. The lipid content of SVF-EVs was compared with SVF using Oil Red O staining. The morphology and adipogenic-related protein of SVF-EVs were characterized. The pro-adipogenic potency of SVF-EVs in vitro was determined using Oil Red O staining of ADSCs, western blot, and qRT-PCR. In vivo, dermal particle grafts mixed with SVF-EVs were subcutaneously transplanted in nude mice and harvested after 4 and 6 weeks. By examining the weight and volume of grafts and histological staining, we explored the effect of SVF-EVs on adipose tissue regeneration and anti-inflammatory ability. Results: Our results showed that the removal rate of proceeding of SVF-EVs could remove 75.07 ± 2.80% lipid in SVF. The SVF-EVs displayed 100 ~ 150 nm sphere vesicles and contained pro-adipogenic protein. In vitro, SVF-EVs promote the synthesis of lipids in ADSCs. Besides, after co-transplanting of SVF-EVs, adipose regeneration was detected in vivo in the dermal particle grafts. Conclusions: These findings revealed that extruding SVF into nanovesicles can effectively reduce the implantation of lipid droplets that cause inflammation, and co-transplanting SVF-EVs with dermal microparticles may be a considerable strategy for large volume defects repair. [ABSTRACT FROM AUTHOR] more...

Exosomes are extracellular nanovesicles secreted by all cell types and have been studied to understand and treat many human diseases. Exosomes are involved in numerous physiological and pathological processes, intercellular communication, and the transfer of substances. Over the years, several studies have explored mammalian-derived exosomes for therapeutic and diagnostic uses. Only recently have plant-derived extracellular vesicles (EVs) attracted attention for their ability to overcome many defects associated with using mammalian-derived extracellular vesicles, such as safety and scale-up issues. The ease of large-scale production, low toxicity, low immunogenicity, efficient cellular uptake, high biocompatibility, and high stability of these nanovesicles make them attractive for drug delivery systems. In addition, their native contents of proteins, miRNAs and secondary metabolites could be exploited for pharmaceutical applications in combination with other drugs. The present review intends to provide adequate tools for studying and developing drug delivery systems based on plant-derived EVs. Therefore, indications concerning extraction methods, characterisation, and drug loading will be offered. Their biological composition and content will also be reported. Finally, the current applications of these systems as nanocarriers for pharmacologically active substances will be shown. [ABSTRACT FROM AUTHOR] more...

Background: Cannabidiol (CBD) is a highly lipophilic compound with potential therapeutic applications in neurological disorders. However, its poor aqueous solubility and bioavailability, coupled with instability in physiological conditions, significantly limit its clinical use. Objectives: This study aimed to develop and characterize nanovesicles incorporating Tween 20 to enhance CBD encapsulation, stability, and the performance across the blood–brain barrier (BBB). Methods: Nanovesicles were prepared via thin-film hydration followed by sonication and optimized for size, polydispersity index, and zeta potential. Stability studies were conducted under physiological conditions and during storage at 4 °C. In vitro release studies employed the dialysis bag method, while permeability across the BBB was assessed using PAMPA-BBB and the hCMEC/D3-BBB cell line, characterized for brain endothelial phenotype and largely employed as a model of human blood–brain barrier (BBB) function. Cytotoxicity was evaluated via MTT and LDH assays. Results: The quantification of CBD was carried out by HPLC-DAD and HPLC-MS/MS. Nanovesicles with Tween 20 (VS-CBD) exhibited smaller size (65.27 ± 1.27 nm vs. 90.7 ± 0.2), lower polydispersity (0.230 ± 0.005 vs. 0.295 ± 0.003), and higher stability compared to conventional liposomes (L-CBD). VS-CBD achieved high encapsulation efficiency (96.80 ± 0.96%) and recovery (99.89 ± 0.52%). Release studies showed sustained CBD release with Higuchi model fitting (R2 = 0.9901). Both PAMPA-BBB and hCMEC/D3-BBB cell lines demonstrated an improved controlled permeability of the formulation compared to free CBD. Cytotoxicity tests confirmed the good biocompatibility of VS-CBD formulations. The addition of Tween 20 to nanovesicles enhanced CBD encapsulation, stability, and controlled release. Conclusions: These nanovesicles represent a promising strategy to improve CBD delivery to the brain, offering sustained therapeutic effects and reduced dosing frequency, potentially benefiting the treatment of neurological disorders. [ABSTRACT FROM AUTHOR] more...

Nano-sized vesicles are ubiquitous in vegetables, fruits, and other edible plants. We have successfully prepared nanovesicles (NVs) from over 150 edible plants. These results suggest that the daily intake of NVs from various foods and their roles in food function are promising novel approaches for explaining the health-promoting properties of edible plants. These vesicles contain RNAs, including miRNAs, similar to extracellular NVs, which play pivotal roles in cell-cell communication. Intriguingly, NVs also contain phytochemicals such as polyphenols and carotenoids that are specific to each edible plant. In conclusion, these dietary NVs have the potential to serve as functional packages to deliver RNAs or phytochemicals to target cells across species from plants to humans. [ABSTRACT FROM AUTHOR] more...

The muco-microbiotic layer represents a critical biological frontier in gastroenterology, emphasizing the intricate interplay between the protective mucus, its resident microbiota, and extracellular vesicles. This review explores the functional morphology of the gastric mucosa, focusing on the gastric muco-microbiotic layer, its role as a protective barrier, and its dynamic interaction with some of the most insidious pathogens such as Helicobacter pylori (H. pylori). Highlighting the multifaceted mechanisms of H. pylori pathogenesis, we have delved into bacterial virulence factors, host immune responses, and the microbiota's regulatory effects. Novel therapeutic strategies for H. pylori eradication, including traditional antibiotic therapies and emerging adjuvant treatments like probiotics and probiotic-derived extracellular vesicles, are critically examined. These findings underscore the potential of targeting nanovesicular interactions in the gastric mucosa, proposing a paradigm shift in the management of H. pylori infections to improve patient outcomes while mitigating antibiotic resistance. [ABSTRACT FROM AUTHOR] more...

Objective: To optimize the preparation method of Hericium erinaceus-derived extracellular nanovesicles and investigate their antioxidant activity and protective effect against oxidative damage in Caco-2 cells. Methods: Hericium erinaceus-derived extracellular nanovesicles (HEDENVs) were isolated from fresh Hericium erinaceus by ultracen- trifugation and sucrose gradient ultracentrifugation. The optimal extraction process of HEDENVs was optimized by oneway test and response surface test, while the particle size, Zeta potential, and morphology of HEDENVs were characterized by a laser particle size instrument and transmission electron microscope. Lipidomics and proteomics analysis of HEDENVs was performed by liquid chromatography-mass spectrometry. The in vitro antioxidant activity of HEDENVs was evaluated by determining the DPPH, ABTS+, and O2- radical scavenging capacity. A Caco-2 cell oxidative stress damage model was created using H2O2, and changes in ROS content in cells were measured using laser confocal microscopy. Results: The optimal extraction process of HEDENVs was the 25% interface of the sucrose concentration, centrifugation time was 2 h, and centrifugal speed was 86000 r/min, at which the concentration of HEDENVs was 402.24 µg/mL. HEDENVs were nanovesicles with a lipid bilayer membrane, the particle size was 110.7±16.9 nm, PDI=0.551, and the Zeta potential was -14.2 mV. Based on the analysis of lipidomics and proteomics, 346 lipids species and 52 proteins were identified in HEDENVs. The results of in vitro antioxidant test showed that the scavenging rate of 400 µg/mL HEDENVs for DPPH free radical was 94.79%, the scavenging rate for ABTS+ free radical was 96.67%, and the scavenging rate for O2- free radical was 96.83%. An oxidative damage model in Caco-2 cells was established by H2O2, HEDENVs could significantly reduce the production of ROS in damaged cells. Conclusion: It showed that HEDENVs had certain antioxidant activity in various antioxidant experiment. [ABSTRACT FROM AUTHOR] more...

Critical limb ischemia (CLI) poses a substantial and intricate challenge in vascular medicine, necessitating the development of innovative therapeutic strategies to address its multifaceted pathophysiology. Conventional revascularization approaches often fail to adequately address the complexity of CLI, necessitating the identification of alternative methodologies. This review explores uncharted territory beyond traditional therapies, focusing on the potential of two distinct yet interrelated entities: cell-derived extracellular vesicles (EVs) and artificial nanovesicles. Cell-derived EVs are small membranous structures naturally released by cells, and artificial nanovesicles are artificially engineered nanosized vesicles. Both these vesicles represent promising avenues for therapeutic intervention. They act as carriers of bioactive cargo, including proteins, nucleic acids, and lipids, that can modulate intricate cellular responses associated with ischemic tissue repair and angiogenesis. This review also assesses the evolving landscape of CLI revascularization through the unique perspective of cell-derived EVs and artificial nanovesicles. The review spans the spectrum from early preclinical investigations to the latest translational advancements, providing a comprehensive overview of the current state of research in this emerging field. These groundbreaking vesicle therapies hold immense potential for revolutionizing CLI treatment paradigms. [ABSTRACT FROM AUTHOR] more...

Liver cancer is a prevalent form of carcinoma worldwide. A novel chitosan-coated optimized formulation capped with irradiated silver nanoparticles (INops) was fabricated to boost the anti-malignant impact of rosuvastatin calcium (RC). Using a 23-factorial design, eight formulations were produced using the solvent evaporation process. The formulations were characterized in vitro to identify the optimal formulation (Nop). The FTIR spectra showed that the fingerprint region is not superimposed with that of the drug; DSC thermal analysis depicted a negligible peak shift; and XRPD diffractograms revealed the disappearance of the typical drug peaks. Nop had an entrapment efficiency percent (EE%) of 86.2%, a polydispersity index (PDI) of 0.254, a zeta potential (ZP) of −35.3 mV, and a drug release after 12 h (Q12) of 55.6%. The chitosan-coated optimized formulation (CS.Nop) showed significant mucoadhesive strength that was 1.7-fold greater than Nop. Physical stability analysis of CS.Nop revealed negligible alterations in VS, ZP, PDI, and drug retention (DR) at 4 °C. The irradiated chitosan-coated optimized formulation capped with silver nanoparticles (INops) revealed the highest inhibition effect on carcinoma cells (97.12%) compared to the chitosan-coated optimized formulation (CS.Nop; 81.64) and chitosan-coated optimized formulation capped with silver nanoparticles (CS.Nop.AgNPs; 92.41). The bioavailability of CS-Nop was 4.95-fold greater than RC, with a residence time of about twice the free drug. CS.Nop has displayed a strong in vitro–in vivo correlation with R2 0.9887. The authors could propose that novel INop could serve as an advanced platform to improve oral bioavailability and enhance hepatic carcinoma recovery. [ABSTRACT FROM AUTHOR] more...

Objective: To optimize the preparation method of Hericium erinaceus-derived extracellular nanovesicles and investigate their antioxidant activity and protective effect against oxidative damage in Caco-2 cells. Methods: Hericium erinaceus-derived extracellular nanovesicles (HEDENVs) were isolated from fresh Hericium erinaceus by ultracentrifugation and sucrose gradient ultracentrifugation. The optimal extraction process of HEDENVs was optimized by one-way test and response surface test, while the particle size, Zeta potential, and morphology of HEDENVs were characterized by a laser particle size instrument and transmission electron microscope. Lipidomics and proteomics analysis of HEDENVs was performed by liquid chromatography-mass spectrometry. The in vitro antioxidant activity of HEDENVs was evaluated by determining the DPPH, ABTS+, and O2− radical scavenging capacity. A Caco-2 cell oxidative stress damage model was created using H2O2, and changes in ROS content in cells were measured using laser confocal microscopy. Results: The optimal extraction process of HEDENVs was the 25% interface of the sucrose concentration, centrifugation time was 2 h, and centrifugal speed was 86000 r/min, at which the concentration of HEDENVs was 402.24 μg/mL. HEDENVs were nanovesicles with a lipid bilayer membrane, the particle size was 110.7±16.9 nm, PDI=0.551, and the Zeta potential was −14.2 mV. Based on the analysis of lipidomics and proteomics, 346 lipids species and 52 proteins were identified in HEDENVs. The results of in vitro antioxidant test showed that the scavenging rate of 400 μg/mL HEDENVs for DPPH free radical was 94.79%, the scavenging rate for ABTS+ free radical was 96.67%, and the scavenging rate for O2− free radical was 96.83%. An oxidative damage model in Caco-2 cells was established by H2O2, HEDENVs could significantly reduce the production of ROS in damaged cells. Conclusion: It showed that HEDENVs had certain antioxidant activity in various antioxidant experiment. more...

Overcoming the skin barrier is crucial for the treatment of skin infections affecting the deep skin layers. Delivery of therapeutics to these layers is considered the key to efficient treatment. The objective of this study is to develop and investigate a nanovesicular system to improve the penetration of the antibacterial drug, clindamycin, into the skin. The carrier employed in this investigation is a transethosomal carrier consisting of phospholipid nanovesicles that possess flexible and adaptable characteristics due to the inclusion of surfactants and cosolvents like ethanol and propanediol. System characterization by atomic force microscopy and dynamic light scattering revealed the presence of enclosed, spherical nanovesicles. Additional pH measurements indicated that the system is appropriate for topical application. The drug release rate in the in vitro tests was shown to be dependent on the viscosity of the system. The results indicated that higher concentrations of the thickening agent, hydroxypropyl cellulose, led to sustained release characteristics. Furthermore, in vitro penetration experiments indicated an enhanced penetration of clindamycin into the skin tissue as compared to traditional formulations. These findings point towards the significance of the transethosomal carrier in facilitating the penetration of drugs into the epidermis leading to better management of bacterial skin infections. [ABSTRACT FROM AUTHOR] more...

Abstract Background Extracellular vesicles (EVs) and extruded nanovesicles (ENVs) are promising nanovesicles (NVs) for drug delivery. However, the application of these NVs is strongly hindered by their short half-life in the circulation. Macrophages (Mφs) in the liver and spleen contribute to the rapid depletion of NVs, but the underlying mechanism is unclear. Methods By collecting the supernatant of PANC-1 cells and squeezing PANC-1 cells, EVs and ENVs derived from PANC-1 cells were prepared via ultracentrifugation. NVs were subsequently identified via western blot, particle size measurement, and electron microscopy. The distribution of NVs in mouse bodies was observed with a live animal imaging system. Liver Mφs were extracted and isolated after NVs were administered, and transcriptome profiling was applied to determine differentially expressed genes (DEGs). siRNAs targeting interested genes were designed and synthesized. In vitro experiments, Mφs were transfected with siRNA or treated with the corresponding inhibitor, after which NV uptake was recorded. Doxorubicin (DOX) was encapsulated in ENVs using an ultrasound method. PANC-1 cell-derived tumors were established in nude mice in vivo, inhibitor pretreatment or no treatment was administered before intravenous injection of ENVs-DOX, and the therapeutic efficacy of ENVs-DOX was evaluated. Results NVs derived from PANC-1 cells were first prepared and identified. After intravenous injection, most NVs were engulfed by Mφs in the liver and spleen. Seven genes of interest were selected via transcriptome sequencing and validated via RT‒PCR. These results confirmed that the TLR2 signaling pathway is responsible for phagocytosis. siTLR2 and its inhibitor sparstolonin B (SpB) significantly inhibited the internalization of NVs by Mφs and downregulated the activity of the TLR2 pathway. The accumulation of ENVs-DOX in the liver was inhibited in vivo by pretreatment with SpB 40 min before intravenous injection, ultimately delaying tumor progression. Conclusion The TLR2 pathway plays a crucial role in the sequestration of NVs by Mφs. A novel antiphagocytic strategy in which pretreatment of mice with SpB inhibits the clearance of NVs and prolongs their half-life in vivo, thereby improving delivery efficiency, was identified. Graphical Abstract more...

Abstract Objective This study aims to elucidate the mechanisms by which nanovesicles (NVs) transport curcumin(CUR) across the blood–brain barrier to treat hypothalamic neural damage induced by heat stroke by regulating the expression of poly(c)-binding protein 2 (PCBP2). Methods Initially, NVs were prepared from macrophages using a continuous extrusion method. Subsequently, CUR was loaded into NVs using sonication, yielding engineered cell membrane Nanovesicles loaded with curcumin (NVs-CUR), which were characterized and subjected to in vitro and in vivo tracking analysis. Evaluations included assessing the toxicity of NVs-CUR using the MTT assay, evaluating neuroprotection of NVs-CUR against H2O2-induced oxidative stress damage in PC12 cells, examining effects on cell morphology and quantity, and detecting ferroptosis-related markers through Western blot and transmission electron microscopy (TEM). Proteomic analysis was conducted on PC12 cells treated with NVs (n = 3) and NVs-CUR (n = 3) to identify downstream key factors. Subsequently, the expression of key factors was modulated, and rescue experiments were performed to validate the impact of NVs-CUR through the regulation of key factor expression. Furthermore, a mouse model of hypothalamic neural damage induced by heat stroke was established, where CUR, NVs-CUR, and ferroptosis inducer Erastin were administered to observe mouse survival rates, conduct nerve function deficit scoring, perform histological staining, and measure levels of inflammation and oxidative stress factors in hypothalamic tissue. Results NVs-CUR was successfully prepared with excellent stability, serving as an advantageous drug delivery system that effectively targets brain injury sites or neurons both in vitro and in vivo. Subsequent in vitro cell experiments demonstrated the biocompatibility of NVs-CUR, showing superior protective effects against H2O2-induced PC12 cell damage and reduced ferroptosis compared to CUR. Moreover, in the mouse model of hypothalamic neural damage induced by heat stroke, NVs-CUR exhibited enhanced therapeutic effects. Proteomic analysis revealed that NVs-CUR exerted its effects through the regulation of key protein PCBP2; silencing PCBP2 reversed the protective effect of NVs-CUR on neural damage and its inhibition of ferroptosis. Additionally, NVs-CUR regulated solute carrier family 7 member 11 (SLC7A11) expression by PCBP2; overexpression of SLC7A11 reversed the promotion of neural damage and ferroptosis by silencing PCBP2. Animal experiments indicated that ferroptosis inducers reversed the improved survival and nerve function observed with NVs-CUR, silencing PCBP2 reversed the ameliorative effects of NVs-CUR on hypothalamic neural injury induced by heat stroke, and overexpression of SLC7A11 further reversed the adverse effects of silencing PCBP2 on hypothalamic neural injury induced by heat stroke. This suggests that NVs-CUR alleviates hypothalamic neural damage induced by heat stroke by targeting the PCBP2/SLC7A11 axis to reduce neuronal ferroptosis. Conclusion This study successfully developed engineered cell membrane NVs-CUR with neuron-targeting properties. NVs-CUR increased the expression of PCBP2, maintained the stability of SLC7A11 mRNA, reduced ferroptosis, and ultimately alleviated hypothalamic neuroinflammation induced by heatstroke. Graphical Abstract more...

Objective: This study aims to elucidate the mechanisms by which nanovesicles (NVs) transport curcumin(CUR) across the blood–brain barrier to treat hypothalamic neural damage induced by heat stroke by regulating the expression of poly(c)-binding protein 2 (PCBP2). Methods: Initially, NVs were prepared from macrophages using a continuous extrusion method. Subsequently, CUR was loaded into NVs using sonication, yielding engineered cell membrane Nanovesicles loaded with curcumin (NVs-CUR), which were characterized and subjected to in vitro and in vivo tracking analysis. Evaluations included assessing the toxicity of NVs-CUR using the MTT assay, evaluating neuroprotection of NVs-CUR against H2O2-induced oxidative stress damage in PC12 cells, examining effects on cell morphology and quantity, and detecting ferroptosis-related markers through Western blot and transmission electron microscopy (TEM). Proteomic analysis was conducted on PC12 cells treated with NVs (n = 3) and NVs-CUR (n = 3) to identify downstream key factors. Subsequently, the expression of key factors was modulated, and rescue experiments were performed to validate the impact of NVs-CUR through the regulation of key factor expression. Furthermore, a mouse model of hypothalamic neural damage induced by heat stroke was established, where CUR, NVs-CUR, and ferroptosis inducer Erastin were administered to observe mouse survival rates, conduct nerve function deficit scoring, perform histological staining, and measure levels of inflammation and oxidative stress factors in hypothalamic tissue. Results: NVs-CUR was successfully prepared with excellent stability, serving as an advantageous drug delivery system that effectively targets brain injury sites or neurons both in vitro and in vivo. Subsequent in vitro cell experiments demonstrated the biocompatibility of NVs-CUR, showing superior protective effects against H2O2-induced PC12 cell damage and reduced ferroptosis compared to CUR. Moreover, in the mouse model of hypothalamic neural damage induced by heat stroke, NVs-CUR exhibited enhanced therapeutic effects. Proteomic analysis revealed that NVs-CUR exerted its effects through the regulation of key protein PCBP2; silencing PCBP2 reversed the protective effect of NVs-CUR on neural damage and its inhibition of ferroptosis. Additionally, NVs-CUR regulated solute carrier family 7 member 11 (SLC7A11) expression by PCBP2; overexpression of SLC7A11 reversed the promotion of neural damage and ferroptosis by silencing PCBP2. Animal experiments indicated that ferroptosis inducers reversed the improved survival and nerve function observed with NVs-CUR, silencing PCBP2 reversed the ameliorative effects of NVs-CUR on hypothalamic neural injury induced by heat stroke, and overexpression of SLC7A11 further reversed the adverse effects of silencing PCBP2 on hypothalamic neural injury induced by heat stroke. This suggests that NVs-CUR alleviates hypothalamic neural damage induced by heat stroke by targeting the PCBP2/SLC7A11 axis to reduce neuronal ferroptosis. Conclusion: This study successfully developed engineered cell membrane NVs-CUR with neuron-targeting properties. NVs-CUR increased the expression of PCBP2, maintained the stability of SLC7A11 mRNA, reduced ferroptosis, and ultimately alleviated hypothalamic neuroinflammation induced by heatstroke. [ABSTRACT FROM AUTHOR] more...

Background: Bile salts enriched nanovesicles (bilosomes) have been attention worthy in the past few years due to their distinctive effect on the enhancement of drug delivery through various physiological administration routes. Oral delivery of multifunctioning phytochemical curcumin has faced a lot of difficulties due to its scarce solubility and poor oral bioavailability. Objective: The current investigation aimed to develop curcumin loaded bilosomes for improvement of oral curcumin bioavailability with maximum efficiency and safety. Methods: The effect of formulation variables (type of span, SDC % to total lipid content Span/Cholesterol molar ratio) on physicochemical characterization and in vitro drug release in simulated intestinal fluid was investigated. Furthermore, in-vivo protective effect of bilosomes on hepatic and renal functions was also studied. Results: and conclusion. The results revealed that the best curcumin loaded bilosomal formulation showed spherical nanovesicular morphology with particle size 145.1 ± 19.42 nm with highly reasonable %EE (93%), Zeta potential (≥ -30mv), prominent controlled in-vitro release reaching 55.18 ± 1.10 after 96 h. The formulation also showed good storage stability with negligible differences in physical features and content. The IC50 values of bilosomal, niosomal, and free curcumin were 216.50, 211.44, and 121.63 mmol/ml, respectively revealing that the unencapsulated curcumin displayed high toxicity on Caco2 cell line (nearly 2 folds). Additionally, the prepared bilosomes showed significant in-vivo hepatic and renal protection in liver cirrhosis induced rats with conservation to all liver and renal markers and histopathological morphology. The study assumes the effectiveness and safety of oral delivery of curcumin loaded bile salts stabilized nanovesicles and its powerful commandment for further investigations. [ABSTRACT FROM AUTHOR] more...

[Display omitted] Glioma is a prevalent brain malignancy associated with poor prognosis. Although chemotherapy serves as the primary treatment for brain tumors, its effectiveness is hindered by the limited ability of drugs to traverse the blood–brain barrier (BBB) and the development of drug resistance linked to tumor hypoxia. Herein, we report the creation of hybrid camouflaged multifunctional nanovesicles comprising membranes of tumor C6 cells (mT) and bacterial outer membrane vesicles (OMVs) and co-loaded with manganese dioxide nanoparticles (MnO 2 NPs) and doxorubicin (DOX) to synergistically enhance the chemotherapy/chemodynamic therapy (CDT) of glioma. Owing to OMV-mediated BBB penetration and mT-inherited tumor-homing properties, MnO 2 -DOX@mT/OMVs can penetrate the BBB and enhance the tumor cell-specific uptake of DOX via "proton sponge effect"-mediated lysosomal escape. This enhances the apoptotic effect induced by DOX and minimizing DOX-associated cardiotoxicity by facilitating the accumulation of DOX at the tumor site. Furthermore, the MnO 2 NPs in MnO 2 -DOX@mT/OMVs can generate potent CDT by accelerating the Fenton-like reaction with DOX-generated H 2 O 2 and achieving glutathione (GSH)-depletion-induced glutathione peroxidase 4 (GPX4) inactivation. These results showed that MnO 2 -DOX@mT/OMVs, designed for brain tumor targeting, significantly inhibited tumor growth and exhibited favorable biological safety. This innovative approach offers the augmentation of anticancer treatment efficacy via a potential combination of chemotherapy and CDT. [ABSTRACT FROM AUTHOR] more...

Background/Objectives: Horseradish (Armoracia rusticana L.) roots—largely used in traditional medicine for their multiple therapeutic effects—are a rich source of health-promoting phytochemicals. However, their efficacy can be compromised by low chemical stability and poor bioavailability. Incorporation into phospholipid vesicles is often proposed to tackle this problem. Methods: In this study, a hydroalcoholic extract was produced from horseradish roots. The extract was characterized by UPLC-MS and HPLC-PDA and formulated in conventional liposomes and Penetration Enhancer-containing Vesicles (PEVs) for skin application. Results: The obtained nanovesicles were small in size (<100 nm), negatively charged, uni/bilamellar, and with high values of entrapment efficiency (>85%) for the flavonoids identified in the extract. Both the free and the nanoformulated extract showed optimal biocompatibility, measured as the absence of hemolysis of erythrocytes and absence of cytotoxicity in skin cell lines. Furthermore, the nanoformulations displayed antioxidant activity in vitro. Conclusions: The proposed nananoformulations could be exploited to counteract oxidative stress involved in the pathogenesis and progression of numerous skin disorders. [ABSTRACT FROM AUTHOR] more...

Membrane vesicles isolated from vegetable tissues have shown promise in encapsulation technologies used in industries like food and cosmetics, offering innovative approaches to product development. However, their associated linked metabolites have not been studied. Lemon vesicle research not only adds value to the lemon crop (Citrus × limon L.), one of the most widely cultivated fruit trees in the world, is a source of bioactive compounds such as phenolics and organic acids. In this study, the influence of elicitation with ZnSO4 and methyl jasmonate, which modulate the bioactive metabolites, on fruit membrane vesicle bond metabolites was studied. The study showed that foliar application of ZnSO4 increased phenolic compounds as caffeic, sinapic, and chlorogenic acids and the flavonoid hesperidin by about 20% in lemons. Furthermore, a clear interaction between vesicles and citrate and ascorbate that were increased by methyl jasmonate were associated with their higher bioactivity. This was related to the double intrinsic in vitro antioxidant activities of these vesicles. [ABSTRACT FROM AUTHOR] more...

Extracellular vesicles (EVs), secreted by almost all living cells, have gained significant attention for their role in intercellular communication and their potential as versatile carriers for biotherapeutics. However, the clinical translation of EV-based therapies faces significant challenges, primarily due to the lack of efficient methods for loading biotherapeutic agents into EVs. This study introduces a simple, reproducible strategy for the simultaneous incorporation of various biotherapeutics within EVs. The process is gentle and preserves the essential physicochemical and biological characteristics of EVs, thereby protecting labile ligands from premature degradation and elimination. The binding and uptake efficiency of EVs by target cells reached approximately 97 % within 24 h of incubation. Administration of EVs loaded with oligodeoxynucleotides (ODN) resulted in a 4-fold increase in IFNγ+ CD4+ T cells and a 5-fold increase in IFNγ+ CD8+ T cells in the spleens and lymph nodes. Additionally, the co-administration of EVs with ODN and ovalbumin (OVA) induced elevated Th1-biased antibody responses and antigen-specific cytotoxic T-cell responses, providing long-lasting complete protection in 60 % of mice against T-cell thymoma challenge. Furthermore, EVs associated with three different ligands (OVA, CpG-ODN, and α-GalCer) effectively regressed established murine melanoma and significantly improved survival rates in mice. This study presents a powerful and promising approach to overcoming the limitations of EV-based cancer vaccines, advancing the development of effective cancer immunotherapies. Immunization with EVs that are co-associated with antigen and biotherapeutic cargo through a lyophilization-based technique elicits potent anti-cancer immunity. [Display omitted] [ABSTRACT FROM AUTHOR] more...

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic and highly fatal disease characterized by excessive accumulation of extracellular matrix (ECM), foci of myofibroblasts, and a usual pattern of interstitial pneumonia. As suggested by international guidelines, the treatment for this disease involves supportive therapies, as there is currently no effective treatment. Plant-derived nanovesicles have emerged as a new treatment for various diseases and have been tested in cellular and murine models. Methods and results: This research aimed to test the use of Allium sativum nanovesicles (AS-NV) in a murine model of IPF induced by bleomycin. AS-NV reduced the amount of collagen and restored lung architecture in the mouse model. AS-NV was tested on human lung fibroblasts, which do not affect the viability of healthy cells. AS-NV treatment decreases the mRNA levels of genes related to fibrosis, inflammation, and ECM deposition (Mmp2,Timp-2,Vegf,Pcna,Col1a1,Tgf-β,α-Sma,IL-1β,and Hif1a) in bleomycin-induced idiopathic pulmonary fibrosis. Conclusions: This research highlights the anti-inflammatory and antifibrotic activity of AS-NV, which contributes to plant nanovesicle mechanisms in IPF; however, more AS-NV studies are needed to identify alternative treatments for idiopathic pulmonary fibrosis. [ABSTRACT FROM AUTHOR] more...

Exosomes are a kind of nanoscale membrane vesicles that can be secreted by many types of cells in both normal and pathological states and play a very important role in intercellular information exchange and transmission by transporting proteins, nucleic acids, lipids, and other biologically active substances to act on the receptor cells. Recent studies have shown that exosomes from some plants, animals, microorganisms, and other food sources can also be extracted like the structure of exosomes secreted by mammalian cells, which are named food-derived exosomes (FDEs) and can be absorbed by intestinal cells and further transported to other organs through blood circulation. With the advantages of high biocompatibility, low immunogenicity, low toxicity, high cargo capacity, and the ability to cross biological barriers, FDEs can be involved in a variety of applications such as immune response, cell migration, and tumor invasion, and have attracted a lot of attention as biotherapeutic agents and drug delivery carriers in the treatment of human diseases. This article reviews the classification, preparation characterization, physiological processes in the human body, biological functions, and application prospects of FDEs. It aims to provide a reference for the research and application of FDEs in disease treatment. [ABSTRACT FROM AUTHOR] more...

[Display omitted] Preventing breast cancer liver metastasis presents formidable challenges with multifaceted obstacles. In the case of acute and chronic liver injury, the disrupted liver microenvironment induced by activated hepatic stellate cells (aHSCs) would suppress immune surveillance and license the re-multiplication of disseminated tumor cells (DTCs). Herein, a cyclic peptide pPB modified nanovesicle with aHSCs targeting capability was constructed as CP-SB-siRNA to co-deliver hydrophobic SB431542 and nucleic acid drug CXCL12 siRNA. Due to the TGF-β signaling inhibition of SB431542, CP-SB-siRNA significantly suppressed the expression levels of genes coding the uppermost fibrosis-associated proteins including α-sma , Col-1 and Col-3 in aHSCs. On the other hand, the gene and protein expression level of metastasis-associated chemokine CXCL12 was significantly decreased. In addition, CP-SB-siRNA could regain the function of NK cells and attenuate the breast cancer proliferation through CXCL12-CXCR4 axis. On both breast cancer spontaneous metastasis with fibrosis mouse model and breast cancer via hematogenous metastasis with fibrosis mouse model, CP-SB-siRNA successfully reversed hepatic fibrosis by regressing aHSCs, and thereby restored the liver microenvironment, ultimately inhibiting breast cancer hepatic metastasis. This nanomaterial vector, featuring targeting and drug co-delivery functionalities, exhibited a great potential to restrain breast cancer hepatic metastasis based on the relationship among aHSCs, NK cells and DTCs. [ABSTRACT FROM AUTHOR] more...

Aim: To identify an optimized strategy for the large‐scale production of nanovesicles (NVs) that preserve the biological properties of exosomes (EXOs) for use in periodontal regeneration. Materials and Methods: NVs from dental follicle stem cells (DFSCs) were prepared through extrusion, and EXOs from DFSCs were isolated. The yield of both extruded NVs (eNVs) and EXOs were quantified through protein concentration and particle number analyses. Their pro‐migration, pro‐proliferation and pro‐osteogenesis capacities were compared subsequently in vitro. Additionally, proteomics analysis was conducted. To further evaluate the periodontal regeneration potential of eNVs and EXOs, they were incorporated into collagen sponges and transplanted into periodontal defects in rats. In vivo imaging and H&E staining were utilized to verify their biodistribution and safety. Micro‐Computed Tomography analysis and histological staining were performed to examine the regeneration of periodontal tissues. Results: The yield of eNVs was nearly 40 times higher than that of EXOs. Interestingly, in vitro experiments indicated that the pro‐migration and pro‐proliferation abilities of eNVs were superior, and the pro‐osteogenesis potential was comparable to EXOs. More importantly, eNVs exhibited periodontal regenerative potential similar to that of EXOs. Conclusions: Extrusion has proven to be an efficient method for generating numerous eNVs with the potential to replace EXOs in periodontal regeneration. [ABSTRACT FROM AUTHOR] more...

Multiple sclerosis (MS) is a complex autoimmune disease with multiple players. In particular, peripheral (myelin-reactive CD4+ T lymphocytes) and central immune cells (microglia) are involved in the neuroinflammatory process and are found in MS brain lesions. New nanotechnological approaches that can cross the blood-brain barrier and specifically target the key players in the disease using biocompatible nanomaterials with low immunoreactivity represent an important challenge. To this end, nanoparticles and nanovesicles have been studied to induce immune tolerance to a wide range of myelin-derived antigens as potential approaches against MS. To this aim, we extracted myelin from bovine brain and produced myelin-based nanovesicles (MyVes) by nanoprecipitation. MyVes have a diameter of about 100 nm, negative zeta potential and contain the typical proteins of the myelin sheath. The results showed that MyVes are not cytotoxic, are hemocompatibile and do not induce an inflammatory response. In vitro experiments showed that MyVes are specifically taken up by microglial cells and are able to induce the expression of the anti-inflammatory cytokine IL-4. In addition, we have used biodistribution experiments to show that MyVes are able to reach the brain after intranasal administration. Finally, MyVes induced the production of the anti-inflammatory cytokines IL-10 and IL-4 in peripheral blood mononuclear cells isolated from MS patients. Taken together, these data provide proof of concept that MyVes may represent a safe nanosystem capable of promoting anti-inflammatory effects by modulating both central and peripheral immune cells to treat neuroinflammation in MS. Recently, nanoparticles and nanovesicles have been investigated as potential approaches for the treatment of neurodegenerative diseases. We propose the use of myelin nanovesicles (MyVes) as a potential application to counteract neuroinflammation in multiple sclerosis (MS). Approximately 2.8 million people worldwide are estimated to live with MS. It is an autoimmune disease directed toward various myelin-derived antigens. Both peripheral immune cells (lymphocytes) and central immune cells (microglia) actively contribute to MS brain lesions. MyVes, due to their myelin nature, specific characteristics (size, zeta potential, and presence of myelin proteins), biocompatibility, and ability to cross the blood-brain barrier, could represent the first nanosystem capable of promoting anti-inflammatory actions by modulating both central and peripheral immune cells to treat neuroinflammation in MS. [Display omitted] [ABSTRACT FROM AUTHOR] more...

Plant-derived compounds have recently garnered significant interest in the field of medicine due to their rich repertoire of phytochemicals, which holds promise for exploring novel therapies to treat cancer. This study embarks on the first-time investigation of the anti-cancerous effect of onion-derived nanovesicles (ODNVs). ODNVs were isolated employing differential centrifugation followed by ultracentrifugation and subsequent characterization using dynamic light scattering (DLS), field emission scanning electron microscopy (FESEM), and Fourier transform infrared spectroscopy (FTIR). Furthermore, we delineated the anti-cancerous effect of ODNVs on two cancer cell line models HeLa (cervical cancer) and PC-3 (prostate cancer) using MTT assay, DAPI-based DNA damage using immunofluorescence microscopy, colony formation assay, migration assay, cell cycle analysis, and evaluation of apoptosis using flow cytometry and western blotting. The findings revealed dose- and time-dependent anti-proliferative effects of ODNVs on both HeLa and PC3 cell lines, accompanied by selective cytotoxicity against cancer cells. Additional results highlighted that ODNVs prevented colony growth and induced S-phase cell cycle arrest. Apoptosis induction was evaluated through alterations in nuclear morphology and the number of apoptotic cells, which increased significantly after ODNV treatment in both cancer cell lines. Furthermore, annexin V/PI staining evaluation of apoptotic cells by flow cytometry demonstrated that ODNV treatment significantly increased the number of apoptotic cells in both PC-3 and HeLa cells. Finally, Western blot analysis indicated changes in apoptosis-related proteins including bcl-2, bax, and caspase-3, emphasizing that the anti-cancerous effect of ODNVs is attributed to the induction of apoptosis and suggests the unexplored anti-cancerous potential of ODNVs. [ABSTRACT FROM AUTHOR] more...

We wish to bring attention to the critical role of the muco-microbiotic layer, a dynamic and integrated system located at mucosal surfaces. This layer represents a cornerstone of host-microbe interactions, composed of three key components: the mucus, the microbiota, and extracellular nanovesicles (commonly referred to as exosomes). more...

Abstract Interleukin 15 (IL15) is crucial for fostering the survival and proliferation of nature killer (NK) cells and cytotoxic T lymphocytes (CTLs), playing a pivotal role in tumor control. However, IL15 supplementary therapy encounters challenges such as systemic inflammation and non‐specific stimulation of cancer cells. Herein, a nanovesicle termed DoxFILN, comprising a membrane presenting IL15/IL15 receptor α complexes (IL15c) and a core of doxorubicin‐loaded ferritin (Dox‐Fn) are reported. The DoxFILN significantly enhances the densities and activities of intratumoral CTLs and NK cells. Mechanistically, DoxFILN undergoes deshelling in the acidic tumor microenvironment, releasing Dox‐Fn and membrane‐bound IL15c. Dox‐Fn selectively target transferrin receptors on cancerous cells, facilitating intracellular Dox release and inducing immunogenic cell death. Concurrently, membrane‐bound IL15c recognizes and activates IL15 receptor β/γc heterodimers, leading to a remarkable increase in the proliferation and activation of CTLs (16‐fold and 28‐fold) and NK cells (37‐fold and 50‐fold). The IL15‐displaying nanovesicle introduced here holds promise as a potential platform for immunochemotherapy in the treatment of cancer. more...

Meng Zhang,1,2 Qi Yuan,1 Peiwen Wang,1 Fan Zhang,1 Dan Wu,1 He Bai,1 Jieting Liu,1 Haifeng Liu,1 Xiaohuan Yuan1 1College of Life Science, Mudanjiang Medical University, Mudanjiang, People’s Republic of China; 2The First Hospital of Qiqihar, Qiqihar, People’s Republic of ChinaCorrespondence: Xiaohuan Yuan, College of Life Science, Mudanjiang Medical University, No. 3 Tongxiang Road, Mudanjiang, 157011, People’s Republic of China, Tel/Fax +86-453-6984401, Email yuanxiaohuan@mdjmu.edu.cnPurpose: Nanovesicles (NVs) derived from bone mesenchymal stem cells (BMSCs) as drug delivery systems are considered an effective therapeutic strategy for diabetes. However, its mechanism of action remains unclear. Here, we evaluated the efficacy and molecular mechanism of BMSC-derived NVs carrying the curcumin analog H8 (H8-BMSCs-NVs) on hepatic glucose and lipid metabolism in type 2 diabetes (T2D).Subjects and Methods: Mouse BMSCs were isolated by collagenase digestion and H8-BMSCs-NVs were prepared by microvesicle extrusion. The effects of H8-BMSCs-NVs on hepatic glucose and lipid metabolism were observed in a T2D mouse model and a HepG2 cell insulin resistance model. To evaluate changes in potential signaling pathways, the PI3K/AKT/AMPK signaling pathway and expression levels of G6P and PEPCK were assessed by Western blotting.Results: H8-BMSCs-NVs effectively improved lipid accumulation in liver tissues and restored liver dysfunction in T2D mice. Meanwhile, H8-BMSCs-NVs effectively inhibited intracellular lipid accumulation in the insulin resistance models of HepG2 cells. Mechanistic studies showed that H8-BMSCs-NVs activated the PI3K/AKT/AMPK signaling pathway and decreased the expression levels of G6P and PEPCK.Conclusion: These findings demonstrate that H8-BMSCs-NVs improved hepatic glucose and lipid metabolism in T2D mice by activating the PI3K/AKT/AMPK signaling pathway, which provides novel evidence suggesting the potential of H8-BMSCs-NVs in the clinically treatment of T2D patients.Keywords: bone mesenchymal stem cell, nanovesicles, curcumin analogue H8, type 2 diabetes more...

In the area of drug development the solubility of an active ingredient plays a very crucial and vital part and is of the highest significance. Increasing importance is being placed on the research into active ingredient solubilization. The designing of a host guest complex with a compound that has a higher dissolubility profile can work with the solubilization of lipophilic drugs. In this research work optimized nano-carriers were effectively synthesized utilizing thin-film hydration strategies. The drug sulfonated calix[4]resorcinarene blend (1:10) containing ethanol was dispersed and sonicated with an estimated three cycles, at an amplitude 70 with a 20-s interval for an optimized time. The synthesized nanovesicles have an average diameter of 477.7 nm, a higher mono dispersity (PDI-0.282), and a greater loading capacity of the drugs is 95%. Atomic force microscopy in accordance with dynamic light-scattering spectra confirmed the spherical shape of paclitaxel-loaded sulfonated calix[4]resorcinarene nanovesicles. In vitro release of medication from nanovesicles affirmed the extended discharge pattern of drugs with r2 of 0.9902 compared with the commercial formulation available on the market. MTT assay is performed to access the toxicity of the sufonated calix[4]resorcinarene in vitro. IC50 values indicate that synthesized sufonated calix[4]resorcinarene shows better IC50 values than paclitaxel and taxol. The formulated nanovesicles from sulfonated calix[4]resorcinarene showed an ideal size with higher capacity for binding drug and provide better patient compliance, which are positive for their expected application as a modular drug delivery platform for anti-cancer drugs. [ABSTRACT FROM AUTHOR] more...

Androgenic alopecia (AGA) is a highly prevalent form of non-scarring alopecia but lacks effective treatments. Stem cell exosomes have similar repair effects to stem cells, suffer from the drawbacks of high cost and low yield yet. Cell-derived nanovesicles acquired through mechanical extrusion exhibit favorable biomimetic properties similar to exosomes, enabling them to efficiently encapsulate substantial quantities of therapeutic proteins. In this study, we observed that JAM-A, an adhesion protein, resulted in a significantly increased the adhesion and resilience of dermal papilla cells to form snap structures against damage caused by dihydrotestosterone and macrophages, thereby facilitating the process of hair regrowth in cases of AGA. Consequently, adipose-derived stem cells were modified to overexpress JAM-A to produce engineered JAM-A overexpressing nanovesicles (JAM-AOE@NV). The incorporation of JAM-AOE@NV into a thermosensitive hydrogel matrix (JAM-AOE@NV Gel) to effectively addresses the limitations associated with the short half-life of JAM-AOE@NV, and resulted in the achievement of a sustained-release profile for JAM-AOE@NV. The physicochemical characteristics of the JAM-AOE@NV Gel were analyzed and assessed for its efficacy in promoting hair regrowth in vivo and vitro. The JAM-AOE@NV Gel, thus, presents a novel therapeutic approach and theoretical framework for promoting the treatment of low cell adhesion diseases similar to AGA. more...

Traditional pesticide emulsion formulation may exert deleterious effects on the environment and even induce stress on nontarget crops in the vicinity. In this study, γ-cyclodextrin (γ-CD)-encapsulated azobenzene derivative nanovesicles were synthesized and loaded with pendimethalin to obtain pendimethalin-loaded γ-CD/azobenzene derivative nanovesicles. Upon exposure to ultraviolet irradiation or sunlight, the azobenzene derivatives are converted from the trans- to cis- configuration, leading to the dissociation of the ternary host–guest complexes, resulting in the vesicle rupture and the subsequent release of pendimethalin. Further investigations were conducted on the γ-CD/azobenzene nanovesicles. According to the release characteristics of herbicides, the release rate of pendimethalin under ultraviolet light (365 nm) or sunlight conditions reached 88.3 ± 3%, which was 4.3 times higher than that under dark conditions, demonstrating excellent photocontrolled release behavior. Pot experiments showed that the herbicidal activity of pendimethalin-loaded nanovesicles against Portulaca oleracea (L.) and Echinochloa crusgalli (L.) Beauv. at the recommended dose was comparable to that of the pendimethalin technical under illuminated conditions. Furthermore, genotoxicity experiments reveal a notable increase in the mitotic index of onion root tip cells treated with pendimethalin-loaded nanovesicles, indicating that it had minimal inhibitory effect on cell metabolism and the genotoxicity was lower than that of pendimethalin technical. Pendimethalin-loaded nanovesicles exhibited favorable stability and photoresponsive performance. These findings reveal a promising avenue for responsive material design and release modulation using such nanovesicle systems, providing insights into their potential applications in targeted pesticide delivery systems. [ABSTRACT FROM AUTHOR] more...

Aim: Polymeric scaffolds were developed fortified with nanovesicle-encapsulated individual curcumin (CUR) and tetrahydrocurcumin (THC) for improved therapeutic efficacy due to their low stability and efficacy in native form. Method: Nanovesicle-encapsulated individual CUR and THC were fabricated using thin-film hydration techniques and characterized. Results & conclusion: CUR/THC in native and vesicle-encapsulated form demonstrated diminished LPS-instigate nitric oxide (NO) levels in macrophage cells in a concentration-dependent demeanor. However, vesicle-encapsulated CUR/THC inhibited NO production at lower concentrations, compared with the native CUR/THC form. Furthermore, the scaffold fortified with vesicle-encapsulated CUR/THC demonstrated improved physical properties with excellent antioxidant, biocompatibility, and human keratinocyte cell proliferation ability. The results recommended that nanovesicle-encapsulated THC can be retained as a potential substitute for CUR with improved therapeutic efficacy. GRAPHICAL ABSTRACT Article highlights Entrapment of curcumin (CUR) and its derivative and tetrahydrocurcumin (THC) within lipid vesicles improved their stability. Entrapment of CUR and THC within lipid vesicles improved cellular compatibility. Entrapment of CUR and THC within lipid vesicles improved intracellular cellular intake. Entrapment of CUR and THC within lipid vesicles attenuated the LPS-induced inflammations. Fortifying lipid-entrapped CUR and THC within polymeric composite improved the therapeutic efficacy and stability. Cellular uptake of lipid-entrapped THC was higher than lipid-entrapped CUR. Fortifying the vesicle-entrapped CUR and THC within polymeric scaffold ameliorated skin keratinocyte migration. [ABSTRACT FROM AUTHOR] more...

Renal ischemia-reperfusion injury (IRI) is one of the most important causes of acute kidney injury (AKI). Interleukin (IL)-37 has been suggested as a novel anti-inflammatory factor for the treatment of IRI, but its application is still limited by its low stability and delivery efficiency. In this study, we reported a novel engineered method to efficiently and easily prepare neutrophil membrane-derived vesicles (N-MVs), which could be utilized as a promising vehicle to deliver IL-37 and avoid the potential side effects of neutrophil-derived natural extracellular vesicles. N-MVs could enhance the stability of IL-37 and targetedly deliver IL-37 to damaged endothelial cells of IRI kidneys via P-selectin glycoprotein ligand-1 (PSGL-1). In vitro and in vivo evidence revealed that N-MVs encapsulated with IL-37 (N-MV@IL-37) could inhibit endothelial cell apoptosis, promote endothelial cell proliferation and angiogenesis, and decrease inflammatory factor production and leukocyte infiltration, thereby ameliorating renal IRI. Our study establishes a promising delivery vehicle for the treatment of renal IRI and other endothelial damage-related diseases. [Display omitted] • Engineered method yields abundant, pure neutrophil membrane nanovesicles efficiently. • N-MVs target injured endothelial cells, avoiding neutrophil vesicle potential side effects. • N-MV@IL-37 enable targeted kidney delivery of IL-37 to counteract IRI. • N-MV@IL-37 mitigate renal IRI by reducing endothelial apoptosis and inflammation. [ABSTRACT FROM AUTHOR] more...

Niosomes are arousing significant interest thanks to their low cost, high biocompatibility, and negligible toxicity. In this work, a supercritical CO2-assisted process was performed at 100 bar and 40 °C to produce niosomes at different Span 80/Tween 80 weight ratios. The formulation of cholesterol and 80:20 Span 80/Tween 80 was selected to encapsulate vancomycin, used as a model active compound, to perform a drug release rate comparison between PEGylated and non-PEGylated niosomes. In both cases, nanometric vesicles were obtained, i.e., 214 ± 59 nm and 254 ± 73 nm for non-PEGylated and PEGylated niosomes, respectively, that were characterized by a high drug encapsulation efficiency (95% for non-PEGylated and 98% for PEGylated niosomes). However, only PEGylated niosomes were able to prolong the vancomycin release time up to 20-fold with respect to untreated drug powder, resulting in a powerful strategy to control the drug release rate. [ABSTRACT FROM AUTHOR] more...

Invasomes and invasomal gel are ultraflexible, soft vesicular, phospholipid based nanocarriers with deeper skin penetration ability for transdermal applications of drugs and phytopharmaceuticals. [ABSTRACT FROM AUTHOR] more...

Background and Objectives: This three-year clinical trial aimed to demonstrate that only the signaling vesicles produced by ADSCa, containing mRNA, microRNA, growth factors (GFs), and bioactive peptides, provide an advantage over classical therapy with adipose disaggregate to make the tissue regeneration technique safer due to the absence of interfering materials and cells, while being extremely minimally invasive. The infiltration of disaggregated adipose nanofat, defined by the Tonnard method, for the regeneration of the dermis and epidermis during physiological or pathological aging continues to be successfully used for the presence of numerous adult stem cells in suspension (ADSCa). An improvement in this method is the exclusion of fibrous shots and cellular debris from the nanofat to avoid inflammatory phenomena by microfiltration. Materials and Methods: A small amount of adipose tissue was extracted after surface anesthesia and disaggregated according to the Tonnard method. An initial microfiltration at 20/40 microns was performed to remove fibrous shots and cellular debris. The microfiltration was stabilized with a sterile solution containing hyaluronic acid and immediately ultrafiltered to a final size of 0.20 microns to exclude the cellular component and hyaluronic acid chains of different molecular weights. The suspension was then injected into the dermis using a mesotherapy technique with microinjections. Results: This study found that it is possible to extract signaling microvesicles using a simple ultrafiltration system. The Berardesca Scale, Numeric Rating Scale (NRS), and Modified Vancouver Scale (MVS) showed that it is possible to obtain excellent results with this technique. The ultrafiltrate can validly be used in a therapy involving injection into target tissues affected by chronic and photoaging with excellent results. Conclusions: This retrospective clinical evaluation study allowed us to consider the results obtained with this method for the treatment of dermal wrinkles and facial tissue furrows as excellent. The method is safe and an innovative regenerative therapy as a powerful and viable alternative to skin regeneration therapies, antiaging therapies, and chronic inflammatory diseases because it lacks the inflammatory component produced by cellular debris and fibrous sprouts and because it can exclude the mesenchymal cellular component by reducing multiple inflammatory cytokine levels. [ABSTRACT FROM AUTHOR] more...