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Nanoparticles (NPs) interact with biological fluids after being injected into the bloodstream. The interactions between NPs and plasma proteins at the nano-bio interface affect their biopharmaceutical properties and distribution in the organ and tissues due to protein corona (PrC) composition, and in turn, modification of the resulting targeting capability. Moreover, lipid and polymer NPs, at their interface, affect the composition of PrC and the relative adsorption and abundance of specific proteins. To investigate this latter aspect, we synthesized and characterized different liposomal formulations (LFs) with lipids and polymer-conjugated lipids at different molar ratios, having different sizes, size distributions and surface charges. The PrC composition of various designed LFs was evaluated ex vivo in human plasma by label-free quantitative proteomics. We also correlated the relative abundance of identified specific proteins in the coronas of the different LFs with their physicochemical properties (size, PDI, zeta potential). The evaluation of outputs from different bioinformatic tools discovered protein clusters allowing to highlight: (i) common as well as the unique species for the various formulations; (ii) correlation between each identified PrC and the physicochemical properties of LFs; (iii) some preferential binding determined by physicochemical properties of LFs; (iv) occurrence of formulation-specific protein patterns in PrC. Investigating specific clusters in PrC will help decode the multivalent roles of the protein pattern components in the drug delivery process, taking advantage of the bio-nanoscale recognition and identification for significant advances in nanomedicine.
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Photothermal therapy combined with chemotherapy has shown great promise in the treatment of cancer. In this synergistic system, a safe, stable, and efficient photothermal agent is desired. Herein, an effective photothermal agent, carbon quantum dots (CQDs), was initially synthesized and then rationally constructed a folic acid (FA)-targeted photothermal multifunctional nanoplatform by encapsulating CQDs and the anticancer drug doxorubicin (DOX) in the liposomes. Indocyanine green (ICG), a near infrared (NIR) photothermal agent, approved by the U.S. Food and Drug Administration, was embedded in the bilayer membrane to further enhance the photothermal effects and facilitate the rapid cleavage of liposomes for drug release. Triggered by the NIR laser, this engineered photothermal multifunctional nanoplatform, not only exhibited an excellent performance with the photothermal conversion efficiency of up to 47.14%, but also achieved controlled release of the payloads. In vitro, and in vivo experiments demonstrated that the photothermal multifunctional nanoplatform had excellent biocompatibility, enhanced tumor-specific targeting, stimuli-responsive drug release, effective cancer cell killing and tumor suppression through multi-modal synergistic therapy. The successful construction of this NIR light-triggered targeted photothermal multifunctional nanoplatform will provide a promising strategy for the design and development of synergistic chemo-photothermal combination therapy and improve the therapeutic efficacy of cancer treatment.
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PEGylation is currently used for the synthesis of stealth liposomes and to enhance the pharmacokinetic and biopharmaceutical properties of payloads. PEGylated dendron phospholipids can decrease the detachment of polyethylene glycol (PEG) from the liposomal surface owing to an increased hydrophobic anchoring effect on the phospholipid bilayer of liposomes and thus generating super stealth liposomes that are suitable for the systemic delivery of anticancer drugs. Herein, doxorubicin hydrochloride-loaded super stealth liposomes were studied for the treatment of breast cancer lung metastasis in an animal model. The results demonstrated that the super stealth liposomes had suitable physicochemical properties for in vivo administration and could significantly increase the efficacy of doxorubicin in breast cancer lung metastasis tumor-bearing mice compared to the free drug. The super stealth liposomes also increased doxorubicin accumulation inside the tumor tissue. The permanence of PEG on the surface of the super stealth liposomes favored the formation of a depot of therapeutic nanocarriers inside the tumor tissue by improving their permanence after stopping treatment. The doxorubicin-loaded super stealth liposomes increased the survival of the mouse tumor model. These promising results demonstrate that the doxorubicin-loaded super stealth liposomes could be an effective nanomedicine to treat metastatic breast cancer.
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Neoplasias de la Mama , Doxorrubicina , Liposomas , Polietilenglicoles , Doxorrubicina/química , Doxorrubicina/farmacología , Doxorrubicina/administración & dosificación , Doxorrubicina/análogos & derivados , Animales , Liposomas/química , Polietilenglicoles/química , Polietilenglicoles/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Femenino , Ratones , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/secundario , Humanos , Línea Celular Tumoral , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/farmacocinética , Ratones Endogámicos BALB C , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/farmacología , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacocinéticaRESUMEN
Deformable nanovesicles have a crucial role in topical drug delivery through the skin, due to their capability to pass intact the stratum corneum and epidermis (SCE) and significantly increase the efficacy and accumulation of payloads in the deeper layers of the skin. Namely, lipid-based ultradeformable nanovesicles are versatile and load bioactive molecules with different physicochemical properties. For this reason, this study aims to make oleic acid based nanovesicles (oleosomes) for the codelivery of icariin and sodium naproxen and increase their permeation through the skin. Oleosomes have suitable physicochemical properties and long-term stability for a potential dermal or transdermal application. The inclusion of oleic acid in the lipid bilayer increases 3-fold the deformable properties of oleosomes compared to conventional liposomes and significantly improves the percutaneous permeation of icariin and sodium naproxen through the human SCE membranes compared to hydroalcoholic solutions of both drugs. The tolerability studies on human volunteers demonstrate that oleosomes are safer and speed up the recovery of transepidermal water loss (TEWL) baselines compared to saline solution. These results highlight promising properties of icariin/sodium naproxen coloaded oleosomes for the treatment of skin disorders and suggest the potential future applications of these nanovesicles for further in vivo experiments.
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Cerebrovascular impairment represents one of the main causes of death worldwide with a mortality rate of 5.5 million per year. The disability of 50% of surviving patients has high social impacts and costs in long period treatment for national healthcare systems. For these reasons, the efficacious clinical treatment of patients, with brain ischemic stroke, remains a medical need. To this aim, a liposome nanomedicine, with monosialic ganglioside type 1 (GM1), OX26 (an anti-transferrin receptor antibody), and CDP-choline (a neurotrophic drug) (CDP-choline/OX26Lip) was prepared. CDP-choline/OX26Lip were prepared by a freeze and thaw method and then extruded through polycarbonate filters, to have narrow size distributed liposomes of ~80 nm. CDP-choline/OX26Lip were stable in human serum, they had suitable pharmacokinetic properties, and 30.0 ± 4.2% of the injected drug was still present in the blood stream 12 h after its systemic injection. The post-ischemic therapeutic effect of CDP-choline/OX26Lip is higher than CDP-choline/Lip, thus showing a significantly high survival rate of the re-perfused post-ischemic rats, i.e. 96% and 78% after 8 days. The treatment with CDP-choline/OX26Lip significantly decreased the peroxidation rate of ~5-times compared to CDP-choline/Lip; and the resulting conjugated dienes, that was 13.9 ± 1.1 mmol/mg proteins for CDP-choline/Lip and 3.1 ± 0.8 for CDP-choline/OX26Lip. OX26 increased the accumulation of GM1-liposomes in the brain tissues and thus the efficacious of CDP-choline. Therefore, this nanomedicine may represent a strategy for the reassessment of CDP-choline to treat post-ischemic events caused by brain stroke, and respond to a significant clinical need.
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Citidina Difosfato Colina , Liposomas , Animales , Citidina Difosfato Colina/administración & dosificación , Citidina Difosfato Colina/farmacocinética , Masculino , Ratas , Humanos , Ratas Sprague-Dawley , Isquemia Encefálica/tratamiento farmacológico , Gangliósido G(M1)/administración & dosificaciónRESUMEN
Atherosclerosis still represents a major driver of cardiovascular diseases worldwide. Together with accumulation of lipids in the plaque, inflammation is recognized as one of the key players in the formation and development of atherosclerotic plaque. Systemic anti-inflammatory treatments are successful in reducing the disease burden, but are correlated with severe side effects, underlining the need for targeted formulations. In this work, curcumin is chosen as the anti-inflammatory payload model and further loaded in lignin-based nanoparticles (NPs). The NPs are then coated with a tannic acid (TA)- Fe (III) complex and further cloaked with fragments derived from platelet cell membrane, yielding NPs with homogenous size. The two coatings increase the interaction between the NPs and cells, both endothelial and macrophages, in steady state or inflamed status. Furthermore, NPs are cytocompatible toward endothelial, smooth muscle and immune cells, while not inducing immune activation. The anti-inflammatory efficacy is demonstrated in endothelial cells by real-time quantitative polymerase chain reaction and ELISA assay where curcumin-loaded NPs decrease the expression of Nf-κb, TGF-ß1, IL-6, and IL-1ß in lipopolysaccharide-inflamed cells. Overall, due to the increase in the cell-NP interactions and the anti-inflammatory efficacy, these NPs represent potential candidates for the targeted anti-inflammatory treatment of atherosclerosis.
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Antiinflamatorios , Aterosclerosis , Plaquetas , Curcumina , Nanopartículas , Curcumina/química , Curcumina/farmacología , Aterosclerosis/tratamiento farmacológico , Humanos , Nanopartículas/química , Plaquetas/metabolismo , Plaquetas/efectos de los fármacos , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antiinflamatorios/administración & dosificación , Animales , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Células Endoteliales de la Vena Umbilical Humana , Taninos/química , Taninos/farmacología , Células RAW 264.7 , Ratones , Macrófagos/efectos de los fármacos , Macrófagos/metabolismoRESUMEN
Bacterial infections pose a significant threat to human health and safety, necessitating the urgent resolution of the problem through the development and implementation of highly effective antibacterial agents. However, the emergence of multidrug-resistant bacteria has diminished the satisfactory effectiveness of antibacterial treatments. To overcome this obstacle, we developed effective antibacterial agents by chemical reduction for inhibiting bacterial proliferation and inducing membrane damage. Specifically, four different types of chitosan/Ag nanoparticle (CS-AgNPs-i) (i-1, 2, 3, 4) complexes were synthesized by varying the quantity of chitosan added during the synthesis process. We found that the amount of CS does not affect the morphology and size of CS-AgNPs-i, which remained at approximately 20 nm and all CS-AgNPs were mostly spherical. The zeta potential measurements indicated that the surface of CS-AgNPs carries a positive charge. Notably, elevating the chitosan concentration led to a more pronounced antibacterial impact, particularly evident in its interaction with the peptidoglycan layer on the bacterial surface. Our experimental results undeniably establish the potent antibacterial efficacy of CS-AgNPs against both Escherichia coli and Staphylococcus aureus. Employing live/dead bacterial staining, we reveal the marked capability of CS-AgNPs to effectively hinder bacterial proliferation. Furthermore, our experimental investigations revealed that CS-AgNPs possess broad-spectrum antimicrobial activity. The results of in vitro cytotoxicity experiments substantiated the high biocompatibility of CS-AgNPs with elevated chitosan loading. The study provides valuable insights into the development of nano-antibacterial agents that exhibit significant potential as a substitute to replace traditional antibiotics for medical applications.
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Quitosano , Nanopartículas del Metal , Humanos , Plata/farmacología , Plata/química , Nanopartículas del Metal/química , Quitosano/farmacología , Quitosano/química , Antibacterianos/farmacología , Antibacterianos/química , Staphylococcus aureus , Escherichia coli , Pruebas de Sensibilidad MicrobianaRESUMEN
Ferroptosis has attracted significant attention as a new mechanism of cell death. Sorafenib (SRF) is widely considered a prototypical ferroptosis-inducing drug, particularly for liver cancer treatment. However, the low solubility and hydrophobic nature of SRF, along with the absence of synergistic therapeutic strategies, still limit its application in cancer treatment. Herein, we report a dual therapeutic method incorporating photothermal therapy and ferroptosis by using Fe-doped mesoporous polydopamine nanoparticles (Fe-mPDA@SRF-TPP) as a carrier for loading SRF and targeting triphenylphosphine (TPP). SRF molecules are efficiently encapsulated within the polydopamine nanospheres with a high loading ratio (80%) attributed to the porosity of Fe-mPDA, and the inherent biocompatibility and hydrophilicity of Fe-mPDA@SRF-TPP facilitate the transport of SRF to the target cancer cells. Under the external stimuli of acidic environment (pH 5.0), glutathione (GSH), and laser irradiation, Fe-mPDA@SRF-TPP shows sustained release of SRF and Fe ions with the ratio of 72 and 50% within 48 h. Fe-mPDA@SRF-TPP nanoparticles induce intracellular GSH depletion, inhibit glutathione peroxidase 4 (GPX4) activity, and generate hydroxyl radicals, all of which are essential components of the therapeutic ferroptosis process for killing MDA-MB-231 cancer cells. Additionally, the excellent near-infrared (NIR) light absorption of Fe-mPDA@SRF-TPP nanoparticles demonstrates their capability for photothermal therapy and further enhances the therapeutic efficiency. Therefore, this nanosystem provides a multifunctional therapeutic platform that overcomes the therapeutic limitations associated with standalone ferroptosis and enhances the therapeutic efficacy of SRF for breast cancer.
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Ferroptosis , Neoplasias Hepáticas , Nanopartículas , Neoplasias , Humanos , Sorafenib/farmacología , Terapia Fototérmica , Hierro , Nanopartículas/química , Neoplasias/terapia , Concentración de Iones de Hidrógeno , Línea Celular TumoralRESUMEN
Despite the efforts and advances done in the last few decades, cancer still remains one of the main leading causes of death worldwide. Nanomedicine and in particular extracellular vesicles are one of the most potent tools to improve the effectiveness of anticancer therapies. In these attempts, the aim of this work is to realize a hybrid nanosystem through the fusion between the M1 macrophages-derived extracellular vesicles (EVs-M1) and thermoresponsive liposomes, in order to obtain a drug delivery system able to exploit the intrinsic tumor targeting capability of immune cells reflected on EVs and thermoresponsiveness of synthetic nanovesicles. The obtained nanocarrier has been physicochemically characterized, and the hybridization process has been validated by cytofluorimetric analysis, while the thermoresponsiveness was in vitro confirmed through the use of a fluorescent probe. Tumor targeting features of hybrid nanovesicles were in vivo investigated on melanoma-induced mice model monitoring the accumulation in tumor site through live imaging and confirmed by cytofluorimetric analysis, showing higher targeting properties of hybrid nanosystem compared to both liposomes and native EVs. These promising results confirmed the ability of this nanosystem to combine the advantages of both nanotechnologies, also highlighting their potential use as effective and safe personalized anticancer nanomedicine.
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Liposomas , Melanoma , Animales , Ratones , Línea Celular Tumoral , Macrófagos , Sistemas de Liberación de MedicamentosRESUMEN
In vitro cell-based characterization methods of nanoparticles are generally static and require the use of secondary analysis techniques and labeling agents. In this study, bare niosomes and chitosan-coated niosomes (chitosomes) and their interactions with intestinal cells are studied under dynamic conditions and without fluorescent probes, using surface plasmon resonance (SPR)-based cell sensing. Niosomes and chitosomes were synthesized by using Tween 20 and cholesterol in a 15 mM:15 mM ratio and then characterized by dynamic light scattering (DLS). DLS analysis demonstrated that bare niosomes had average sizes of â¼125 nm, polydispersity index (PDI) below 0.2, and a negative zeta (ζ)-potential of -35.6 mV. In turn, chitosomes had increased sizes up to â¼180 nm, with a PDI of 0.2-0.3 and a highly positive ζ-potential of +57.9 mV. The viability of HT29-MTX, Caco-2, and Caco-2/HT29-MTX cocultured cells showed that both niosomes and chitosomes are cytocompatible up to concentrations of 31.6 µg/mL for at least 240 min. SPR analysis demonstrated that chitosomes interact more efficiently with HT29-MTX, Caco-2, and Caco-2/HT29-MTX cocultures compared to bare niosomes. The resulting SPR measurements were further supported by confocal microscopy and flow cytometry studies, which demonstrated that this method is a useful complementary or even alternative tool to directly characterize the interactions between niosomes and in vitro cell models in label-free and real-time conditions.
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Quitosano , Liposomas , Humanos , Células CACO-2 , IntestinosRESUMEN
Multidrug resistance (MDR) is currently a big challenge in cancer therapy and limits its success in several patients. Tumors use the MDR mechanisms to colonize the host and reduce the efficacy of chemotherapeutics that are injected as single agents or combinations. MDR mechanisms are responsible for inactivation of drugs and formbiological barriers in cancer like the drug efflux pumps, aberrant extracellular matrix, hypoxic areas, altered cell death mechanisms, etc. Nanocarriers have some potential to overcome these barriers and improve the efficacy of chemotherapeutics. In fact, they are versatile and can deliver natural and synthetic biomolecules, as well as RNAi/DNAi, thus providing a controlled release of drugs and a synergistic effect in tumor tissues. Biocompatible and safe multifunctional biopolymers, with or without specific targeting molecules, modify the surface and interface properties of nanocarriers. These modifications affect the interaction of nanocarriers with cellular models as well as the selection of suitable models for in vitro experiments. MDR cancer cells, and particularly their 2D and 3D models, in combination with anatomical and physiological structures of tumor tissues, can boost the design and preparation of nanomedicines for anticancer therapy. 2D and 3D cancer cell cultures are suitable models to study the interaction, internalization, and efficacy of nanocarriers, the mechanisms of MDR in cancer cells and tissues, and they are used to tailor a personalized medicine and improve the efficacy of anticancer treatment in patients. The description of molecular mechanisms and physio-pathological pathways of these models further allow the design of nanomedicine that can efficiently overcome biological barriers involved in MDR and test the activity of nanocarriers in 2D and 3D models of MDR cancer cells.
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Antineoplásicos , Neoplasias , Humanos , Resistencia a Múltiples Medicamentos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Nanomedicina , Sistemas de Liberación de Medicamentos , Portadores de Fármacos/química , Resistencia a Antineoplásicos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéuticoRESUMEN
Neuroblastoma is a biologically heterogeneous extracranial tumor, derived from the sympathetic nervous system, that affects most often the pediatric population. Therapeutic strategies relying on aggressive chemotherapy, surgery, radiotherapy, and immunotherapy have a negative outcome in advanced or recurrent disease. Here, spherical polymeric nanomedicines (SPN) are engineered to co-deliver a potent combination therapy, including the cytotoxic docetaxel (DTXL) and the natural wide-spectrum anti-inflammatory curcumin (CURC). Using an oil-in-water emulsion/solvent evaporation technique, four SPN configurations were engineered depending on the therapeutic payload and characterized for their physico-chemical and pharmacological properties. All SPN configurations presented a hydrodynamic diameter of â¼ 185 nm with a narrow size distribution. A biphasic release profile was observed for all the configurations, with almost 90 % of the total drug mass released within the first 24 h. SPN cytotoxic potential was assessed on a panel of human neuroblastoma cells, returning IC50 values in the order of 1 nM at 72 h and documenting a strong synergism between CURC and DTXL. Therapeutic efficacy was tested in a clinically relevant orthotopic model of neuroblastoma, following the injection of SH-SY5Y-Luc+ cells in the left adrenal gland of athymic mice. Although â¼ 2 % of the injected SPN per mass tissue reached the tumor, the overall survival of mice treated with CURC/DTXL-SPN was extended by 50 % and 25 % as compared to the untreated control and the monotherapies, respectively. In conclusion, these results demonstrate that the therapeutic potential of the DTXL/CURC combination can be fully exploited only by reformulating these two compounds into systemically injectable nanoparticles.
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Antineoplásicos , Curcumina , Nanopartículas , Neuroblastoma , Niño , Humanos , Ratones , Animales , Docetaxel/farmacología , Neuroblastoma/tratamiento farmacológico , Antineoplásicos/farmacología , Antineoplásicos/química , Polímeros/química , Línea Celular TumoralRESUMEN
Joint diseases are one of the most common causes of morbidity and disability worldwide. The main diseases that affect joint cartilage are osteoarthritis and rheumatoid arthritis, which require chronic treatment focused on symptomatic relief. Conventional drugs administered through systemic or intra-articular routes have low accumulation and/or retention in articular cartilage, causing dose-limiting toxicities and reduced efficacy. Therefore, there is an urgent need to develop improved strategies for drug delivery, in particular, the use of micro- and nanotechnology-based methods. Encapsulation of therapeutic agents in delivery systems reduces drug efflux from the joint and protects against rapid cellular and enzymatic clearance following intra-articular injection. Consequently, the use of drug delivery systems decreases side effects and increases therapeutic efficacy due to enhanced drug retention in the intra-articular space. Additionally, the frequency of intra-articular administration is reduced, as delivery systems enable sustained drug release. This review summarizes various advanced drug delivery systems, such as nano- and microcarriers, developed for articular cartilage diseases.
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Artritis Reumatoide , Cartílago Articular , Osteoartritis , Humanos , Sistemas de Liberación de Medicamentos , Osteoartritis/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológicoRESUMEN
The use of proper nanocarriers for dermal and transdermal delivery of anti-inflammatory drugs recently gained several attentions in the scientific community because they pass intact and accumulate payloads in the deepest layers of skin tissue. Ascorbyl palmitate-based vesicles (aspasomes) can be considered a promising nanocarrier for dermal and transdermal delivery due to their skin whitening properties and suitable delivery of payloads through the skin. The aim of this study was the synthesis of multidrug Idebenone/naproxen co-loaded aspasomes for the development of an effective anti-inflammatory nanomedicine. Aspasomes had suitable physicochemical properties and were safe inâ vivo if topically applied on human healthy volunteers. Idebenone/naproxen co-loaded aspasomes demonstrated an increased therapeutic efficacy of payloads compared to the commercially available Naprosyn® gel, with a rapid decrease of chemical-induced erythema on human volunteers. These promising results strongly suggested a potential application of Idebenone/naproxen multidrug aspasomes for the development of an effective skin anti-inflammatory therapy.
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Naproxeno , Absorción Cutánea , Administración Cutánea , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Sistemas de Liberación de Medicamentos , Humanos , Naproxeno/metabolismo , Naproxeno/farmacología , Naproxeno/uso terapéutico , Piel/metabolismo , Ubiquinona/análogos & derivadosRESUMEN
Oral insulin delivery could change the life of millions of diabetic patients as an effective, safe, easy-to-use, and affordable alternative to insulin injections, known by an inherently thwarted patient compliance. Here, we designed a multistage nanoparticle (NP) system capable of circumventing the biological barriers that lead to poor drug absorption and bioavailability after oral administration. The nanosystem consists of an insulin-loaded porous silicon NP encapsulated into a pH-responsive lignin matrix, and surface-functionalized with the Fc fragment of immunoglobulin G, which acts as a targeting ligand for the neonatal Fc receptor (FcRn). The developed NPs presented small size (211 ± 1 nm) and narrow size distribution. The NPs remained intact in stomach and intestinal pH conditions, releasing the drug exclusively at pH 7.4, which mimics blood circulation. This formulation showed to be highly cytocompatible, and surface plasmon resonance studies demonstrated that FcRn-targeted NPs present higher capacity to interact and being internalized by the Caco-2 cells, which express FcRn, as demonstrated by Western blot. Ultimately, in vitro permeability studies showed that Fc-functionalized NPs induced an increase in the amount of insulin that permeated across a Caco-2/HT29-MTX co-culture model, showing apparent permeability coefficients (P app ) of 2.37 × 10-6 cm/s, over the 1.66 × 10-6 cm/s observed for their non-functionalized counterparts. Overall, these results demonstrate the potential of these NPs for oral delivery of anti-diabetic drugs.
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The natural healing capacity of the tendon tissue is limited due to the hypovascular and cellular nature of this tissue. So far, several conventional approaches have been tested for tendon repair to accelerate the healing process, but all these approaches have their own advantages and limitations. Regenerative medicine and tissue engineering are interdisciplinary fields that aspire to develop novel medical devices, innovative bioscaffold, and nanomedicine, by combining different cell sources, biodegradable materials, immune modulators, and nanoparticles for tendon tissue repair. Different studies supported the idea that bioscaffolds can provide an alternative for tendon augmentation with an enormous therapeutic potentiality. However, available data are lacking to allow definitive conclusion on the use of bioscaffolds for tendon regeneration and repairing. In this review, we provide an overview of the current basic understanding and material science in the field of bioscaffolds, nanomedicine, and tissue engineering for tendon repair.
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Extracellular vesicles (EVs) are cell-released lipid-bilayer nanoparticles that contain biologically active cargo involved in physiological and pathological intercellular communication. In recent years, the therapeutic potential of EVs has been explored in various disease models. In particular, mesenchymal stromal cell-derived EVs have been shown to exert anti-inflammatory, anti-oxidant, anti-apoptotic, and pro-angiogenic properties in cardiovascular, metabolic and orthopedic conditions. However, a major drawback of EV-based therapeutics is scale-up issues due to extensive cell culture requirements and inefficient isolation protocols. An emerging alternative approach to time-consuming and costly cell culture expansion is to obtain therapeutic EVs directly from the body, for example, from plasma and adipose tissue. This review discusses isolation methods and therapeutic applications of plasma and adipose tissue-derived EVs, highlighting advantages and disadvantages compared to cell culture-derived ones.
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In the last few decades, the combination between nanotechnology and nutraceutics has gained the attention of several research groups. Nutraceuticals are considered as active compounds, abundant in natural products, showing beneficial effects on human health. Unfortunately, the uses, and consequently the health benefits, of many nutraceutical products are limited by their unsuitable chemico-physical features. For example, many nutraceuticals are characterized by low water solubility, low stability and high susceptibility to light and oxygen, poor absorption and potential chemical modifications after their administration. Based on the potential efficacy of nutraceuticals and on their limiting features, nanotechnology could be considered a revolutionary innovation in empowering the beneficial properties of nutraceuticals on human health, thus enhancing their efficacy in several diseases. For this reason, nanotechnology could represent a new frontier in supplementary food. In this review, the most recent nanotechnological approaches are discussed, focusing on their ability to improve the bioavailability of the most common nutraceuticals, providing an overview regarding both the advantages and the possible limitations of the use of several nanodelivery systems. In fact, although the efficacy of smart nanocarriers in improving health benefits deriving from nutraceuticals has been widely demonstrated, the conflicting opinions on the mechanism of action of some nanosystems still reduce their applicability in the therapeutic field.
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Unraveling the proteins interacting with nanoparticles (NPs) in biological fluids, such as blood, is pivotal to rationally design NPs for drug delivery. The protein corona (PrC), formed on the NP surface, represents an interface between biological components and NPs, dictating their pharmacokinetics and biodistribution. PrC composition depends on biological environments around NPs and on their intrinsic physicochemical properties. We generated different formulations of non-ionic surfactant/non-phospholipid vesicles, called niosomes (NIOs), using polysorbates which are biologically safe, cheap, non-toxic and scarcely immunogenic. PrC composition and relative protein abundance for all designed NIOs were evaluated ex vivo in human plasma (HP) by quantitative label-free proteomics. We studied the correlation of the relative protein abundance in the corona with cellular uptake of the PrC-NIOs in healthy and cancer human cell lines. Our results highlight the effects of polysorbates on nano-bio interactions to identify a protein pattern most properly aimed to drive the NIO targeting in vivo, and assess the best conditions of PrC-NIO NP uptake into the cells. This study dissected the biological identity in HP of polysorbate-NIOs, thus contributing to shorten their passage from preclinical to clinical studies and to lay the foundations for a personalized PrC.