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Dasatinib (DAS) is an oral tyrosine kinase inhibitor; however, its efficacy is significantly subsided by its low oral bioavailability. The present research aimed to improve DAS's oral delivery and efficacy in triple-negative breast cancer by fabricating its mucoadhesive lecithin-chitosan hybrid nanoparticles (DAS-L/CS-NPs). DAS-L/CS-NPs were optimized using Box-Behnken design which showed mean particle size and percent entrapment efficiency of 179.7 ± 5.42 nm and 64.65 ± 0.06 %, respectively. DAS-L/CS-NPs demonstrated sustained release profile in different release media up to 48 h and showed 10 times higher apparent permeability coefficient and flux than free DAS suspension. The binding of DAS-L/CS-NPs to the mucus layer was demonstrated via ex-vivo mucoadhesion study and change in absorbance using turbidimetry. In cell culture studies, DAS-L/CS-NPs revealed a 4.14-fold decrease in IC50, significantly higher cellular uptake and mitochondrial membrane depolarization, 3.82-fold increased reactive oxygen species generation and 2.10-fold enhanced apoptosis in MDA-MB-231 cells than free DAS. In in-vivo pharmacokinetic assessment, DAS-L/CS-NPs showed a 5.08-fold and 3.74-fold rise in AUC (0-t) and Cmax than free DAS suspension, respectively. An acute toxicity study revealed a good safety profile of DAS-L/CS-NPs. In a nutshell, proposed hybrid nanoparticles are promising carriers for improved oral delivery of poorly water-soluble drugs.
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Quitosano , Nanopartículas , Portadores de Fármacos/farmacocinética , Lecitinas , Dasatinib , Tamaño de la PartículaRESUMEN
Virus-like particle (VLP) vaccine is considered to be the most promising candidate alternative to the traditional inactivated vaccine for foot-and-mouth disease (FMD). To elicit a desired immune response, hollow mesoporous silica nanoparticles (HMSNs) have been synthesized and utilized as a nanocarrier for FMD VLP vaccine delivery. The as-prepared HMSNs displayed a relatively small particle size (â¼260 nm), large cavity (â¼150 nm), and thin wall (â¼55 nm). The inherent structural superiorities make them ideal nanocarriers for the FMD VLP vaccine, which exhibited good biocompatibility, great protein-loading capacity, high antibody-response level, and protective efficiency, even comparable to commercial adjuvant ISA 206. All the results suggested that HMSNs may be a valid nanocarrier in VLP-based vaccines.
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Virus de la Fiebre Aftosa , Fiebre Aftosa , Nanopartículas , Vacunas , Animales , Dióxido de Silicio/química , Fiebre Aftosa/prevención & control , Nanopartículas/químicaRESUMEN
BACKGROUND: Cancer is characterized as the leading cause of death, and the susceptibility of cancer cells to develop resistance due to long-term exposure to complementary chemotherapeutic treatment is referred to as multidrug resistance cancer cells (MDRC), which is a significant obstacle in the treatment of malignancies. Since complementary medicine lost its effectiveness, the development of potential alternative and novel therapeutic approaches has been elevated to a top priority in recent years. In this context, a bioactive protein lectin from plant and animal sources exhibits an invaluable source of anticancer agents with vast therapeutic potential. PURPOSE: This manuscript's primary purpose is to enlighten the evidence-based (from 1986 to 2022) possible molecular mechanism of alternative treatment approaches using lectins over the complementary medicines used for cancer treatment. METHODS: The PRISMA rules have been followed properly and qualitative and quantitative data are synthesized systematically. Articles were identified based on Clinical and preclinical reports published on lectin that investigated the in-depth cellular mechanisms, of reverse drug integrative oncology, as a nano-carried targeted delivery. Articles were systematically screened from 1986 to 2022 and selected based on electronic database searches, Medline (PubMed), Google Scholar, Web of Science, Encyclopaedias, Scopus, and ClinicalTrials.gov database. RESULTS: The search turned up 4,212 publications from 38 different nations, of which 170 reference articles were used in our analysis, in 16 combination therapy and their mode of action, and 27 clinical trial studies including dosage and mechanism of action were included. Reports from the 30 lectins belonging to 28 different families have been included. The reversal mechanism of lectin and alternative therapy against MDRC is critically screened and according to a few clinical and preclinical reports, lectin can suppress the overexpressing genes like P-53, EGFR, and P-gp, MRP, and ABC transporter proteins associated with intracellular transportation of drugs. Since, the drug efflux mechanism leads to MDRC, in this phenomenon, lectin plays a key role in reversing the efflux mechanism. Few preclinical reports have mentioned that lectin shows synergism in combination with complementary medicine and as a nano drug carrier helps to deliver to the targeted site. CONCLUSION: We have discussed the alternative therapy using lectin and an in-depth insight into the reversal drug resistance mechanisms to combat MDRC cancer, enhance the efficacy, reduce toxicity and adverse events, and ensure targeted delivery, and their application in the field of cancer diagnosis and prognosis has been discussed. However, further investigation is necessary in drug development and clinical trials which could be helpful to elaborate the reversal mechanism and unlock newer treatment modalities in MDRC cancer.
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Antineoplásicos , Neoplasias , Animales , Humanos , Resistencia a Múltiples Medicamentos , Lectinas/farmacología , Lectinas/uso terapéutico , Resistencia a Antineoplásicos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Neoplasias/tratamiento farmacológicoRESUMEN
The role of herbal medicines in the treatment of viruses and the identification of potential antiviral drugs has been the focus of researchers for decades. The control and treatment of viral diseases are very important due to the evolution of viruses and the emergence of new viruses compared to other pathogens such as fungi and bacteria. Astragalus membranaceus (AM) is a significant medicinal plant. The potential use of this plant and its chemical components in the treatment of inflammatory illnesses and viral diseases has been vigorously researched recently. Astragalus polysaccharides (APS) make up the majority of AM's ingredients. The main mechanisms of the antiviral effect of APS have been investigated in some studies. The results of these studies show that APS can exert its antiviral effect by enhancing type I IFN signaling, inhibiting the expression of Bax and Caspase-3 proteins in the apoptosis pathway, and other antiviral mechanisms such as anti-inflammatory activities. The most well-known inflammatory products of APS's antiviral effects are B-cell proliferation, antibody products, nuclear factor-kappa B (NF-κB), and IL(s). Although it has a known effectiveness, there are some limitations to this substance's use as medicine. The use of nanotechnology is removing these limitations and its ability to be used as an anti-virus agent. The purpose of this review is to emphasize the role of AM, especially APS, in controlling inflammatory pathways in the treatment of viral infections. With the emergence of these herbal medications, a new path has been opened in the control and treatment of viral infections.
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Plantas Medicinales , Virosis , Astragalus propinquus/química , Transducción de Señal , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antivirales/farmacología , Antivirales/uso terapéutico , Virosis/tratamiento farmacológico , Polisacáridos/farmacología , Polisacáridos/uso terapéuticoRESUMEN
Traditional Chinese Medicines (TCMs) have been used for centuries for the treatment and management of various diseases. However, their effective delivery to targeted sites may be a major challenge due to their poor water solubility, low bioavailability, and potential toxicity. Nanocarriers, such as liposomes, polymeric nanoparticles, inorganic nanoparticles and organic/inorganic nanohybrids based on active constituents from TCMs have been extensively studied as a promising strategy to improve the delivery of active constituents from TCMs to achieve a higher therapeutic effect with fewer side effects compared to conventional formulations. This review summarizes the recent advances in nanocarrier-based delivery systems for various types of active constituents of TCMs, including terpenoids, polyphenols, alkaloids, flavonoids, and quinones, from different natural sources. This review covers the design and preparation of nanocarriers, their characterization, and in vitro/vivo evaluations. Additionally, this review highlights the challenges and opportunities in the field and suggests future directions for research. Nanocarrier-based delivery systems have shown great potential in improving the therapeutic efficacy of TCMs, and this review may serve as a comprehensive resource to researchers in this field.
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Medicamentos Herbarios Chinos , Nanopartículas , Medicamentos Herbarios Chinos/farmacología , Medicina Tradicional China , Disponibilidad Biológica , Nanotecnología , Sistemas de Liberación de MedicamentosRESUMEN
Blueberries are fruits known for their high level of anthocyanins, which have high nutritional value and several biological properties. However, the chemical instability of anthocyanins is one of the major limitations of their application. The stability of blueberry anthocyanin extracts (BAEs) encapsulated in a ferritin nanocarrier was investigated in this study for several influencing parameters, including pH, temperature, UV-visible light, redox agents, and various metal ions. The outcomes supported the positive role of protein nanoparticles in enhancing the stability of blueberry anthocyanins by demonstrating that the stability of encapsulated BAE nanoparticles with ferritin carriers was significantly higher than that of free BAEs and a mixture of BAEs and ferritin carriers. This study provides an alternative approach for enhancing blueberry anthocyanin stability using ferritin nanocarrier encapsulation.
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Antocianinas , Arándanos Azules (Planta) , Antocianinas/química , Arándanos Azules (Planta)/química , Ferritinas , Extractos Vegetales/química , Luz , Frutas/químicaRESUMEN
In this work, chitosan (CS), Starch (S), and Molybdenum Disulfide (MoS2) were combined to create a nanocarrier that was utilized to treat breast cancer using the MCF-7 cell line. To analyze the features of the nanocarrier, Fourier-transform infrared spectroscopy (FTIR) and X-Ray diffraction (XRD) tests were performed, respectively, to discover physical interactions and chemical bonding. Field emission scanning electron microscopy (FE-SEM), Dynamic light scattering (DLS), and zeta potential analyses were performed and reported to determine the structural characteristics and morphology of nanoparticles, size distribution, and surface charge of nanocarriers, respectively. The average size of the nanocomposite was measured at around 279 nm, and the surface charge of the nanocarrier was determined to be +86.31 mV. The entrapment and drug loading efficiency of nanocarriers were 87.25 % and 46.5 %, respectively, which is an acceptable value. The kinetics and release mode of the drug were investigated, and it was found that the synthesized nanocarrier was sensitive to pH and that its release was stable. The amount of the nanocarriers' toxicity and cell death were evaluated using MTT tests and flow cytometry, respectively. In the present study, the nanocarrier was wholly nontoxic and had anticancer properties against the MCF-7 cell line. This nanocarrier is very important due to its non-toxicity and sensitivity to pH and can be used in drug delivery and medical applications.
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Neoplasias de la Mama , Quitosano , Curcumina , Nanocompuestos , Nanopartículas , Humanos , Femenino , Curcumina/química , Quitosano/química , Neoplasias de la Mama/tratamiento farmacológico , Almidón , Molibdeno , Nanopartículas/química , Nanocompuestos/química , Concentración de Iones de Hidrógeno , Liberación de Fármacos , Portadores de Fármacos/química , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
Cancer cells show unique redox homeostasis. Glutathione (GSH) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) play essential roles as coenzymes of multiple key antioxidant enzymes. Coenzyme depletion offers a unique opportunity for cancer treatment by inducing oxidative stress. Here, we report an innovative hybrid nanocarrier for cancer redox therapy via selective depletion of GSH and NADPH. The nanocarrier core is a sorafenib-loaded porous zeolitic imidazole framework (ZIF-65), and the shell is epigallocatechin gallate (EGCG)-Fe3+ complex (EF). The nitroimidazole ligand in ZIF-65 could selectively deplete NADPH under hypoxia. Sorafenib diminished GSH by inhibiting cystine import and GSH biosynthesis. EGCG can reduce Fe3+ to Fe2+, which aids the generation of hydroxyl radicals via the Fenton reaction. The reversible coordination between nitroimidazole and Zn2+, EGCG, and Fe3+ enables triggered cargo release in acidic lysosomes. Tailored nanocarriers induced the depletion of both coenzymes (GSH and NADPH) and boosted reactive oxygen species in a 4T1 murine cancer cell line. The altered redox balance eventually resulted in efficient apoptotic cell death. The current work offers a novel means of redox cancer therapy via the selective depletion of key antioxidant enzymes in hypoxic cells.
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Neoplasias , Nitroimidazoles , Ratones , Humanos , Animales , Coenzimas/metabolismo , NADP/metabolismo , Antioxidantes/metabolismo , Sorafenib , Oxidación-Reducción , Glutatión/metabolismo , Hipoxia , Línea Celular Tumoral , Neoplasias/tratamiento farmacológicoRESUMEN
Among 17 Panax species identified across the world, Panax ginseng (Korean ginseng), Panax quinquefolius (American ginseng), and Panax notoginseng (Chinese ginseng) are highly recognized for the presence of bioactive compound, ginsenosides and their pharmacological effects. P. ginseng is widely used for synthesis of different types of nanoparticles compared to P. quinquefolius and P. notoginseng. The use of nano-ginseng could increase the oral bioavailability, membrane permeability, and thus provide effective delivery of ginsenosides to the target sites through transport system. In this review, we explore the synthesis of ginseng nanoparticles using plant extracts from various organs, microbes, and polymers, as well as their biomedical applications. Furthermore, we highlight transporters involved in transport of ginsenoside nanoparticles to the target sites. Size, zeta potential, temperature, and pH are also discussed as the critical parameters affecting the quality of ginseng nanoparticles synthesis.
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Ginsenósidos , Panax , Humanos , Ginsenósidos/farmacología , Panax/química , Extractos Vegetales/químicaRESUMEN
5-Fluorouracil (5-FU) is a cytotoxic drug with a low half-life. These features can cause some problems such as burst drug release and numerous side effects. In the present study, a pH-sensitive nanocomposite of polyvinylpyrrolidone (PVP)/carboxymethyl cellulose (CMC)/γ-alumina developed by using water in oil in water (W/O/W) double emulsion method. The fabricated emulsion has been employed as the 5-FU carrier to investigate its effects on drug half-life, side effects, drug loading efficiency (DLE), and drug entrapment efficiency (DEE). Analyzing the FTIR and XRD indicated the successful loading of 5-FU into the nanocarrier and affirmed the synthesized nanocomposite's chemical bonding and crystalline features. Furthermore, by using DLS and Zeta potential assessment, size and undersize distribution, as well as the stability of the drug-loaded nanocomposite were determined, which demonstrated the monodisperse and stable nanoparticles. Moreover, the nanocomposites with spherical shapes and homogeneous surfaces were shown in FE-SEM, which indicated good compatibility for the constituents of the nanocomposites. Moreover, by employing BET analysis the porosity has been investigated. Drug release pattern was studied, which indicated a controlled drug release behavior with above 96 h drug retention. Besides, the loading and entrapment efficiencies were obtained 44 % and 86 %, respectively. Furthermore, the curve fitting technique has been employed and the predominant release mechanism has been determined to evaluate the best-fitted kinetic models. MTT assay and flow cytometry assessment has been carried out to investigate the cytotoxic effects of the fabricated drug-loaded nanocomposite on MCF-7 and normal cells. The results showed enhanced cytotoxicity and late apoptosis for the PVP/CMC/γ-alumina/5-FU. Based on the MTT assay outcomes on normal cell lines (L929), which indicated above 90 % cell viability, the biocompatibility and biosafety of the synthesized nanocarrier have been confirmed. Moreover, due to the porosity of the PVP/CMC/γ-alumina, this nanocarrier can exploit from high specific surface area and be more sensitive to environmental conditions such as pH. These outcomes propose that the novel pH-sensitive PVP/CMC/γ-alumina nanocomposite can be a potential candidate for drug delivery applications, especially for cancer therapy.
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Antineoplásicos , Fluorouracilo , Fluorouracilo/química , Carboximetilcelulosa de Sodio/química , Porosidad , Povidona , Óxido de Aluminio/farmacología , Emulsiones , Agua , Concentración de Iones de Hidrógeno , Portadores de Fármacos/química , Liberación de FármacosRESUMEN
Nanocarrier antigen-drug delivery system interacts specifically with immune cells and provides intelligent delivery modes to improve antigen delivery efficiency and facilitate immune progression. However, these nanoparticles often have weak adhesion to cells, followed by insufficient cell absorption, leading to a failed immune response. Inspired by the structure and function of viruses, virus-like mesoporous silica nanoparticles (VMSNs) were prepared by simulating the surface structure, centripetal-radialized spike structure and rough surface topology of the virus and co-acted with the toll-like receptor 7/8 agonist imiquimod (IMQ) and antigens oocyte albumin (OVA). Compared to the conventional spherical mesoporous silica nanoparticles (MSNs), VMSNs which was proven to be biocompatible in both cellular and in vivo level, had higher cell invasion ability and unique endocytosis pathway that was released from lysosomes and promoted antigen cross-expression. Furthermore, VMSNs effectively inhibited B16-OVA tumor growth by activating DCs maturation and increasing the proportion of CD8+ T cells. This work demonstrated that virus-like mesoporous silica nanoparticles co-supply OVA and IMQ, could induce potent tumor immune responses and inhibit tumor growth as a consequence of the surface spike structure induces a robust cellular immune response, and undoubtedly provided a good basis for further optimizing the nanovaccine delivery system.
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Nanopartículas , Neoplasias , Humanos , Linfocitos T CD8-positivos , Dióxido de Silicio/química , Biomimética , Internalización del Virus , Antígenos , Nanopartículas/química , Adyuvantes Inmunológicos , Inmunoterapia , PorosidadRESUMEN
Changes in weather conditions and lifestyle lead to an annual increase in the amount of lung cancer, and therefore it is one of the three most common types of cancer, making it important to find an appropriate treatment method. This research aims to introduce a new smart nano-drug delivery system with antibacterial and anticancer capabilities that could be applied for the treatment of lung cancer. It is composed of a niosomal carrier containing curcumin as an anticancer drug and is coated with a chitosan polymeric shell, alongside Rose Bengal (RB) as a photosensitizer with an antibacterial feature. The characterization results confirmed the successful fabrication of lipid-polymeric carriers with a size of nearly 80 nm and encapsulation efficiency of about 97% and 98% for curcumin and RB, respectively. It had the Korsmeyer-Peppas release pattern model with pH and temperature responsivity so that nearly 60% and 35% of RB and curcumin were released at 37 °C and pH 5.5. Moreover, it showed nearly 50% toxicity against lung cancer cells over 72 h and antibacterial activity against Escherichia coli. Accordingly, this nanoformulation could be considered a candidate for the treatment of lung cancer; however, in vivo studies are needed for better confirmation.
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Oral diseases, such as dental caries, periodontitis and oral cancer, have a very high morbidity over the world. Basically, many oral diseases are commonly related to bacterial infections or cell malignant proliferation, and usually located on the superficial positions. These features allow the convenient and efficient application of photodynamic therapy (PDT) for oral diseases, since PDT is ideally suitable for the diseases on superficial sites and has been widely used for antimicrobial and anticancer therapy. Photosensitizers (PSs) are an essential element in PDT, which induce the generation of a large number of reactive oxygen species (ROS) upon absorption of specific lights. Almost all the PSs are small molecules and commonly suffered from various problems in the PDT environment, such as low solubility and poor stability. Recently, reports on the nanomedicine-based PDT have been well documented. Various functionalized nanomaterials can serve either as the PSs carriers or the direct PSs, thus enhancing the PDT efficacy. Herein, we aim to provide a comprehensive understanding of the features of different oral diseases and discuss the potential applications of nanomedicine-based PDT in the treatment of some common oral diseases. Also, the concerns and possible solutions for nanomaterials-mediated PDT are discussed.
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Caries Dental , Enfermedades de la Boca , Nanoestructuras , Fotoquimioterapia , Humanos , Caries Dental/tratamiento farmacológico , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Enfermedades de la Boca/tratamiento farmacológicoRESUMEN
Pancreatic cancer is one of the harshest and most challenging cancers to treat, often labeled as incurable. Chemotherapy continues to be the most popular treatment yet yields a very poor prognosis. The main barriers such as inefficient drug penetration and drug resistance, have led to the development of drug carrier systems. The benefits, ease of fabrication and modification of liposomes render them as ideal future drug delivery systems. This review delves into the versatility of liposomes to achieve various mechanisms of treatment for pancreatic cancer. Not only are there benefits of loading chemotherapy drugs and targeting agents onto liposomes, as well as mRNA combined therapy, but liposomes have also been exploited for immunotherapy and can be programmed to respond to photothermal therapy. Multifunctional liposomal formulations have demonstrated significant pre-clinical success. Functionalising drug-encapsulated liposomes has resulted in triggered drug release, specific targeting, and remodeling of the tumor environment. Suppressing tumor progression has been achieved, due to their ability to more efficiently and precisely deliver chemotherapy. Currently, no multifunctional surface-modified liposomes are clinically approved for pancreatic cancer thus we aim to shed light on the trials and tribulations and progress so far, with the hope for liposomal therapy in the future and improved patient outcomes. STATEMENT OF SIGNIFICANCE: Considering that conventional treatments for pancreatic cancer are highly associated with sub-optimal performance and systemic toxicity, the development of novel therapeutic strategies holds outmost relevance for pancreatic cancer management. Liposomes are being increasingly considered as promising nanocarriers for providing not only an early diagnosis but also effective, highly specific, and safer treatment, improving overall patient outcome. This manuscript is the first in the last 10 years that revises the advances in the application of liposome-based formulations in bioimaging, chemotherapy, phototherapy, immunotherapy, combination therapies, and emergent therapies for pancreatic cancer management. Prospective insights are provided regarding several advantages resulting from the use of liposome technology in precision strategies, fostering new ideas for next-generation diagnosis and targeted therapies of pancreatic cancer.
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Antineoplásicos , Neoplasias Pancreáticas , Humanos , Liposomas , Antineoplásicos/uso terapéutico , Sistemas de Liberación de Medicamentos , Portadores de Fármacos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias PancreáticasRESUMEN
Although quercetin (QC) has valuable advantages, its low water solubility and poor permeability have limited its utilization as an anticancer drug. In this study, hydrogel nanocomposite of chitosan (CS), halloysite (HNT), and graphiticcarbon nitride (g-C3N4) was prepared and loaded by QC using a water in oil in water emulsification process to attain QC sustained-release. Using g-C3N4 in the HNT/CS hydrogel solution enhanced the entrapment effectiveness (EE %) by up to 86 %. The interactions between QC and nanoparticles caused the nanocomposite pH-responsive behavior that assists in minimizing the side effect of the anticancer agent by controlling the burst release of QC at neutral conditions. According to DLS analysis, the size of the QC-loaded nanovehicle was 454.65 nm, showing that nanoparticles are highly monodispersed, which also was approved by FE-SEM. Additionally, Zeta potential value for the fabricated drug-loaded nanocarrier is +55.23 mV displaying that nanoparticles have good stability. The hydrogel nanocomposite structure's completeness was shown by FTIR pattern, and quercetin was included into the designed delivery system based on XRD data. Besides, the drug release profile indicated that a targeted sustained-release and pH-sensitive release of anticancer drug with the 96-hour extended-release were noticed. In order to comprehend the process of QC release at pH 5.4 and 7.4, four kinetic models were employed to find the best-suited model according to the acquired release data. Finally, the MTT experiment revealed considerable cytotoxicity against breast cancer cells, MCF-7 cell line was experimented in vitro, for the CS/HNT/g-C3N4 targeted delivery system in comparison to QC as a free drug. According to the above description, the CS/HNT/g-C3N4 delivery platform is a unique pH-sensitive drug delivery system for anticancer purposes that improves loading as well as sustained-release of quercetin.
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Antineoplásicos , Quitosano , Nanopartículas , Neoplasias , Humanos , Células MCF-7 , Quercetina/farmacología , Arcilla , Preparaciones de Acción Retardada/farmacología , Concentración de Iones de Hidrógeno , Sistemas de Liberación de Medicamentos , Antineoplásicos/farmacología , Liberación de Fármacos , Portadores de FármacosRESUMEN
Hepatic fibrosis is a chronic liver disease that lacks effective pharmacotherapeutic treatments. As part of the disease's mechanism, hepatic stellate cells (HSCs) are activated by damage-related stimuli to secrete excessive extracellular matrix, leading to collagen deposition. Currently, the drug delivery system that targets HSCs in the treatment of liver fibrosis remains an urgent challenge due to the poor controllability of drug release. Since the level of reactive oxygen species (ROS) increases sharply in activated HSCs (aHSCs), we designed ROS-responsive micelles for the HSC-specific delivery of a traditional Chinese medicine, resveratrol (RES), for treatment of liver fibrosis. The micelles were prepared by the ROS-responsive amphiphilic block copolymer poly(l-methionine-block-Nε-trifluoro-acetyl-l-lysine) (PMK) and a PEG shell modified with a CRGD peptide insertion. The CRGD-targeted and ROS-responsive micelles (CRGD-PMK-MCs) could target aHSCs and control the release of RES under conditions of high intracellular ROS in aHSCs. The CRGD-PMK-MCs treatment specifically enhanced the targeted delivery of RES to aHSCs both in vitro and in vivo. In vitro experiments show that CRGD-PMK-MCs could significantly promote ROS consumption, reduce collagen accumulation, and avert activation of aHSCs. In vivo results demonstrate that CRGD-PMK-MCs could alleviate inflammatory infiltration, prevent fibrosis, and protect hepatocytes from damage in fibrotic mice. In conclusion, CRGD-PMK-MCs show great potential for targeted and ROS-responsive controlled drug release in the aHSCs of liver fibrosis.
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Células Estrelladas Hepáticas , Micelas , Ratones , Animales , Especies Reactivas de Oxígeno/farmacología , Cirrosis Hepática/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Colágeno/farmacología , HígadoRESUMEN
Although medicinal natural products and their derivatives have shown promising effects in disease therapies, they usually suffer the drawbacks in low solubility and stability in the physiological environment, low delivery efficiency, side effects due to multi-targeting, and low site-specific distribution in the lesion. In this review, targeted delivery was well-guided by liposomal formulation in the aspects of preparation of functional liposomes, liposomal medicinal natural products, combined therapies, and image-guided therapy. This review is believed to provide useful guidance to enhance the targeted therapy of medicinal natural products and their derivatives.
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Light-responsive nanocarrier-based drug delivery systems (NDDSs), due to their unique advantages such as safety, minimal cross-reaction, and spatiotemporal precision, have received wide attention. Notably, second near-infrared (NIR-II) light, which has a high penetration depth for manipulating NDDSs to release drugs, is in high demand. Herein, polyethylene glycol (PEG)-modified hollow CuxS nanoparticles (NPs) are developed as an all-in-one NIR-II light-responsive NDDS for synergistic chemo-photothermal therapy. First, CuxS-PEG NPs were prepared under mild conditions by using Cu2O NPs as sacrificial templates. The morphology, photothermal effect, drug loading/releasing abilities, and synergistic chemo-photothermal therapy of CuxS-PEG NPs have been investigated. The CuxS-PEG NPs with hollow structures showed a high drug loading capacity (â¼255 µg Dox per mg of CuxS NPs) and stimuli-responsive drug release triggered by NIR-II laser irradiation. The synergistic chemo-photothermal therapy based on the Dox/CuxS-PEG NPs showed 98.5% tumor elimination. Our study emphasizes the great potential of CuxS-PEG NPs as an all-in-one NIR-II light-responsive NDDS for applications in biomedicine.
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Doxorrubicina , Terapia Fototérmica , Sistemas de Liberación de Medicamentos , Rayos Infrarrojos , Fototerapia , Polietilenglicoles/químicaRESUMEN
Liver fibrosis is a chronic disease resulting from repetitive or prolonged liver injury with limited treatment options. Sorafenib has been reported to be a potential antifibrotic agent; however, its therapeutic effect is restricted because of its low bioavailability and severe adverse effects in the gastrointestinal (GI) tract. In this study, we developed sorafenib-loaded silica-containing redox nanoparticles (sora@siRNP) as an oral nanomedicine to treat liver fibrosis. The designed siRNP were prepared by self-assembly of amphiphilic block copolymers, which possess antioxidant nitroxide radicals as a side chain of the hydrophobic segment and porous silica particles in the nanoparticle core. The silica moieties in the core formed a crosslink between the self-assembling block copolymers to afford stable drug absorption, which could be useful in harsh GI conditions after oral drug administration. Based on in vitro evaluation, sora@siRNP exerted antiproliferative and antifibrotic effects against hepatic stellate cells (HSCs) and low toxicity against normal endothelial cells. A pharmacokinetic study showed that siRNP significantly improved the bioavailability and distribution of sorafenib in the liver. In an in vivo study using a mouse model of CCl4-induced liver fibrosis, oral administration of sora@siRNP significantly suppressed the fibrotic area in comparison to free sorafenib administration. In mice with CCl4-induced fibrosis, free sorafenib administration did not suppress the expression of α-smooth muscle actin; however, mice treated with sora@siRNP showed significantly suppressed expression of α-smooth muscle actin, indicating the inhibition of HSC activation, which was confirmed by in vitro experiments. Moreover, oral administration of free sorafenib induced severe intestinal damage and increased leakage into the gut, which can be attributed to the generation of reactive oxygen species (ROS). Our antioxidant nanocarriers, siRNP, reduced the adverse effects of local ROS scavenging in the GI tract. Our results suggest that sora@siRNP could serve as a promising oral nanomedicine for liver fibrosis.
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Nanopartículas , Dióxido de Silicio , Actinas/efectos adversos , Actinas/metabolismo , Antioxidantes/farmacología , Células Endoteliales/metabolismo , Células Estrelladas Hepáticas/metabolismo , Humanos , Hígado/metabolismo , Cirrosis Hepática/patología , Nanopartículas/química , Oxidación-Reducción , Polímeros/química , Especies Reactivas de Oxígeno/metabolismo , Dióxido de Silicio/química , Sorafenib/uso terapéuticoRESUMEN
Nutraceuticals are bioactive or chemical compounds acclaimed for their valuable biological activities and health-promoting effects. The global community is faced with many health concerns such as cancers, cardiovascular and neurodegenerative diseases, diabetes, arthritis, osteoporosis, etc. The effect of nutraceuticals is similar to pharmaceuticals, even though the term nutraceutical has no regulatory definition. The usage of nutraceuticals, to prevent and treat the aforementioned diseases, is limited by several features such as poor water solubility, low bioavailability, low stability, low permeability, low efficacy, etc. These downsides can be overcome by the application of the field of nanotechnology manipulating the properties and structures of materials at the nanometer scale. In this review, the linear and cyclic dextrin, formed during the enzymatic degradation of starch, are highlighted as highly promising nanomaterials- based drug delivery systems. The modified cyclic dextrin, cyclodextrin (CD)-based nanosponges (NSs), are well-known delivery systems of several nutraceuticals such as quercetin, curcumin, resveratrol, thyme essential oil, melatonin, and appear as a more advanced drug delivery system than modified linear dextrin. CD-based NSs prolong and control the nutraceuticals release, and display higher biocompatibility, stability, and solubility of poorly water-soluble nutraceuticals than the CD-inclusion complexes, or uncomplexed nutraceuticals. In addition, the well-explored CD-based NSs pathways, as drug delivery systems, are described. Although important progress is made in drug delivery, all the findings will serve as a source for the use of CD-based nanosystems for nutraceutical delivery. To sum up, our review introduces the extensive literature about the nutraceutical concepts, synthesis, characterization, and applications of the CD-based nano delivery systems that will further contribute to the nutraceutical delivery with more potent nanosystems based on linear dextrins.