RESUMEN
INTRODUCTION: Esophageal cancer is one of the major cancers in China. Most patients with esophageal cancer are diagnosed at an advanced stage, and the 5 year survival rate is discouraging. Combined chemotherapy is a common method for the treatment of esophageal cancer. METHODS: In this study, distearoyl phosphatidyl ethanolamine polyethylene glycol 2000 (DSPE-PEG2000) nanoliposomes (NLPs) encapsulating the anticancer drugs docetaxel (DOX) and oridonin (ORD) were prepared, and their ability to enhance the release of anticancer drugs was determined. The NLP system was characterized by transmission electron microscopy, particle size and encapsulation efficiency. In addition, the release characteristics and pharmacodynamics of these drugs were also studied in detail. RESULTS: When the DOX/ORD ratio was 2:1, the higher proportion of DOX led to a stronger synergy effect. DOX/ORD NLPs were prepared by the high-pressure homogenization method and had a uniform spherical morphology. The mean particle size and polydispersity index were determined to be 246.4 and 0.163, respectively. The stability results showed that no significant change was observed in particle size, zeta potential, Encapsulation efficiency and dynamic light scattering for DOX/ORD NLPs during the observation period. The results of in vitro release illustrated that the acidic environment of tumor might be beneficial to drug release. The three-dimensional tumorsphere showed that DOX/ORD NLPs can reach the interior of tumor spheres, which destroys the structure of cells, resulting in irregular spherical tumor spheres. The in vivo study results indicated that DOX/ORD NLPs had an obvious targeting effect on subcutaneous tumors and have the potential to actively deliver drugs to tumor tissues. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was used to detect apoptosis. The results showed that DOX/ORD NLP treatment could significantly induce apoptosis and inhibit tumor growth. CONCLUSION: The DOX/ORD NLPs prepared in this study can enhance the anti-tumor activity, and are expected to be a promising co-delivery platform for the treatment of esophageal cancer.
Asunto(s)
Diterpenos de Tipo Kaurano , Docetaxel , Neoplasias Esofágicas , Liposomas , Diterpenos de Tipo Kaurano/farmacología , Diterpenos de Tipo Kaurano/química , Diterpenos de Tipo Kaurano/administración & dosificación , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/patología , Docetaxel/farmacología , Docetaxel/administración & dosificación , Docetaxel/química , Liposomas/química , Animales , Humanos , Línea Celular Tumoral , Ratones , Antineoplásicos/farmacología , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Nanopartículas/química , Tamaño de la Partícula , Ensayos Antitumor por Modelo de Xenoinjerto , Liberación de Fármacos , Sistemas de Liberación de Medicamentos/métodos , Ratones Desnudos , Ratones Endogámicos BALB C , Sistema de Administración de Fármacos con Nanopartículas/químicaRESUMEN
BACKGROUND: Colorectal cancer is a common disease worldwide with non-specific symptoms such as blood in the stool, bowel movements, weight loss and fatigue. Chemotherapy drugs can cause side effects such as nausea, vomiting and a weakened immune system. The use of antioxidants such as hesperidin could reduce the side effects, but its low bioavailability is a major problem. In this research, we aimed to explore the drug delivery and efficiency of this antioxidant on the HCT116 colorectal cancer cell line by loading hesperidin into PLGA nanoparticles. MATERIALS AND METHODS: Hesperidin loaded PLGA nanoparticles were produced by single emulsion evaporation method. The physicochemical properties of the synthesized hesperidin-loaded nanoparticles were determined using SEM, AFM, FT-IR, DLS and UV-Vis. Subsequently, the effect of the PLGA loaded hesperidin nanoparticles on the HCT116 cell line after 48 h was investigated by MTT assay at three different concentrations of the nanoparticles. RESULT: The study showed that 90% of hesperidin were loaded in PLGA nanoparticles by UV-Vis spectrophotometry and FT-IR spectrum. The nanoparticles were found to be spherical and uniform with a hydrodynamic diameter of 76.2 nm in water. The release rate of the drug was about 93% after 144 h. The lowest percentage of cell viability of cancer cells was observed at a concentration of 10 µg/ml of PLGA nanoparticles loaded with hesperidin. CONCLUSION: The results indicate that PLGA nanoparticles loaded with hesperidin effectively reduce the survival rate of HCT116 colorectal cancer cells. However, further studies are needed to determine the appropriate therapeutic dosage and to conduct animal and clinical studies.
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Neoplasias Colorrectales , Hesperidina , Nanopartículas , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Humanos , Hesperidina/química , Hesperidina/farmacología , Hesperidina/administración & dosificación , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Neoplasias Colorrectales/tratamiento farmacológico , Células HCT116 , Nanopartículas/química , Supervivencia Celular/efectos de los fármacos , Ácido Láctico/química , Ácido Poliglicólico/química , Sistemas de Liberación de Medicamentos , Tamaño de la Partícula , Portadores de Fármacos/química , Espectroscopía Infrarroja por Transformada de Fourier , Antineoplásicos/farmacología , Antineoplásicos/química , Sistema de Administración de Fármacos con Nanopartículas/químicaRESUMEN
Background: At present, the few photothermal/chemotherapy studies about retinoblastoma that have been reported are mainly restricted to ectopic models involving subcutaneous implantation. However, eyeball is unique physiological structure, the blood-retina barrier (BRB) hinders the absorption of drug molecules through the systemic route. Moreover, the abundant blood circulation in the fundus accelerates drug metabolism. To uphold the required drug concentration, patients must undergo frequent chemotherapy sessions. Purpose: To address these challenges above, we need to develop a secure and effective drug delivery system (FA-PEG-PDA-DOX) for the fundus. Methods: We offered superior therapeutic efficacy with minimal or no side effects and successfully established orthotopic mouse models. We evaluated cellular uptake performance and targeting efficiency of FA-PEG-PDA-DOX nanosystem and assessed its synergistic antitumor effects in vitro and vivo. Biodistribution assessments were performed to determine the retention time and targeting efficiency of the NPs in vivo. Additionally, safety assessments were conducted. Results: Cell endocytosis rates of the FA-PEG-PDA-DOX+Laser group became 5.23 times that of the DOX group and 2.28 times that of FA-PEG-PDA-DOX group without irradiation. The fluorescence signal of FA-PEG-PDA-DOX persisted for more than 120 hours at the tumor site. The number of tumor cells (17.2%) in the proliferative cycle decreased by 61.6% in the photothermal-chemotherapy group, in contrast to that of the saline control group (78.8%). FA-PEG-PDA-DOX nanoparticles(NPs) exhibited favorable biosafety and high biocompatibility. Conclusion: The dual functional targeted nanosystem, with the effects of DOX and mild-temperature elevation by irradiation, resulted in precise chemo/photothermal therapy in nude mice model.
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Doxorrubicina , Indoles , Terapia Fototérmica , Polímeros , Retinoblastoma , Animales , Retinoblastoma/terapia , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacología , Doxorrubicina/administración & dosificación , Ratones , Terapia Fototérmica/métodos , Humanos , Indoles/química , Indoles/farmacocinética , Indoles/farmacología , Línea Celular Tumoral , Polímeros/química , Distribución Tisular , Polietilenglicoles/química , Polietilenglicoles/farmacocinética , Ratones Desnudos , Nanopartículas/química , Sistemas de Liberación de Medicamentos/métodos , Neoplasias de la Retina/terapia , Neoplasias de la Retina/tratamiento farmacológico , Ratones Endogámicos BALB C , Antibióticos Antineoplásicos/farmacología , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/administración & dosificación , Modelos Animales de Enfermedad , Ensayos Antitumor por Modelo de Xenoinjerto , Sistema de Administración de Fármacos con Nanopartículas/química , Sistema de Administración de Fármacos con Nanopartículas/farmacocinéticaRESUMEN
Nanomedicine has been developed to reduce or eliminate the side effects and toxicity upon systemic therapy of chemotherapeutic agents and to improve their therapeutic efficacy. However, the translation of non-sized or nano-encapsulated drugs is hampered by the low penetration and accumulation of engineered nanoparticles (NPs) in sites of tumors as well as their poor pharmacokinetics. This may be due to the synthetic structure of NPs and also complicated and unknown characteristics of the solid tumor microenvironment (TME). As a result, the TME is being better identified, and the interactions between NPs and the TME or human body are being discovered or predicted. These findings have led to the development of more biocompatible, intelligent, and controllable bio-based nanoformulations that could overcome current barriers and provide sufficient drug delivery to the TME, as discussed in this paper. These formulations are designed to (i) modify the surface of NPs to improve blood circulation while reducing their off-target accumulation and side effects in vivo, (ii) pass through the tumor vasculature by modulating or targeting angiogenesis, (iii) promote NPs distribution in solid tumor regions by applying biological/physical stimuli or extracellular matrix remodeling, and (iv) overcome the cell membrane barrier and other compartments of the cell by specific cell targeting to release the payload drug into the cytoplasm or nucleoplasm.
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Neoplasias , Microambiente Tumoral , Humanos , Microambiente Tumoral/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Animales , Nanopartículas/química , Sistemas de Liberación de Medicamentos , Sistema de Administración de Fármacos con Nanopartículas/química , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacocinéticaRESUMEN
Tumor vessels characterized by abnormal functions and structures hinder the infiltration and immune antigen presentation of immune cells by inducing the formation of an immunosuppressive microenvironment ("cold" environment). Vascular-targeted therapy has been proven to enhance immune stimulation and the effectiveness of immunotherapy by modulating the "cold" microenvironment, such as hypoxia and an acidic microenvironment. Notably, a therapeutic strategy based on "vascular-immune" crosstalk can achieve dual regulation of tumor vessels and the immune system by reprogramming the tumor microenvironment (TME), thus forming a positive feedback loop between tumor vessels and the immune microenvironment. From this perspective, we discuss the factors of tumor angiogenesis and "cold" TME formation. Building on this foundation, some vascular-targeted therapeutic drugs will be elaborated upon in detail to achieve dual regulation of tumor vessels and immunity. More importantly, we focus on cutting-edge nanotechnology in view of "vascular-immune" crosstalk and discuss the rational fabrication of tailor-made nanosystems for efficiently enhancing immunotherapy.
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Inmunoterapia , Neoplasias , Neovascularización Patológica , Microambiente Tumoral , Humanos , Neoplasias/terapia , Neoplasias/inmunología , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunología , Inmunoterapia/métodos , Neovascularización Patológica/inmunología , Neovascularización Patológica/terapia , Animales , Sistema de Administración de Fármacos con Nanopartículas/química , Sistemas de Liberación de Medicamentos/métodos , Nanomedicina , Nanopartículas/químicaRESUMEN
Acne is a common chronic inflammatory disorder of the sebaceous gland in the hair follicle. Commonly used external medications cause skin irritation, and the transdermal capacity is weak, making it difficult to penetrate the cuticle skin barrier. Hair follicles can aid in the breakdown of this barrier. As nanomaterials progress, polymer-based nanocarriers are routinely used for hair follicle drug delivery to treat acne and other skin issues. Based on the physiological and anatomical characteristics of hair follicles, this paper discusses factors affecting hair follicle delivery by polymer nanocarriers, summarizes the common combination technology to improve the targeting of hair follicles by carriers, and finally reviews the most recent research progress of different polymer nanodrug-delivery systems for the treatment of acne by targeting hair follicles.
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Acné Vulgar , Portadores de Fármacos , Folículo Piloso , Polímeros , Folículo Piloso/efectos de los fármacos , Folículo Piloso/metabolismo , Acné Vulgar/tratamiento farmacológico , Humanos , Polímeros/química , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos/métodos , Nanopartículas , Administración Cutánea , Animales , Sistema de Administración de Fármacos con Nanopartículas/químicaRESUMEN
Nanoparticle-based systems are extensively investigated for drug delivery. Among others, with superior biocompatibility and enhanced targeting capacity, albumin appears to be a promising carrier for drug delivery. Albumin nanoparticles are highly favored in many disease therapies, as they have the proper chemical groups for modification, cell-binding sites for cell adhesion, and affinity to protein drugs for nanocomplex generation. Herein, this review summarizes the recent fabrication techniques, modification strategies, and application of albumin nanoparticles. We first discuss various albumin nanoparticle fabrication methods, from both pros and cons. Then, we provide a comprehensive introduction to the modification section, including organic albumin nanoparticles, metal albumin nanoparticles, inorganic albumin nanoparticles, and albumin nanoparticle-based hybrids. We finally bring further perspectives on albumin nanoparticles used for various critical diseases.
Albumin appears to be a promising carrier for drug delivery with superior biocompatibility and enhanced targeting capacity. This review focuses on the importance of albumin nanoparticles in drug delivery and concludes the recent fabrication techniques to prepare albumin nanoparticles, the modification strategies to require functional albumin nanoparticles, and critical applications of albumin nanoparticles in various diseases. The aim of this review is to help readers understand the significant potential of albumin nanoparticles in drug delivery.
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Albúminas , Nanopartículas , Humanos , Albúminas/química , Albúminas/administración & dosificación , Nanopartículas/química , Sistemas de Liberación de Medicamentos/métodos , Animales , Portadores de Fármacos/química , Sistema de Administración de Fármacos con Nanopartículas/químicaRESUMEN
OBJECTIVE: Alzheimer's disease (AD), a common degenerative disease of the central nervous system in the elderly, has become the third largest health killer after cardiovascular and cerebrovascular diseases and tumors. Based on the fact that Alzheimer's disease is a disease with multiple etiologies and complex pathology, a single target is bound to have a limited curative effect, and the synergy of multiple links and multiple targets is expected to achieve a better curative effect. The aim of this study is to investigate the brain targeting of a drug modified by chitosan, based on the new nanodrug delivery system for treating Alzheimer's disease developed by the research group. MATERIALS AND METHODS: Chitosan with good biocompatibility, biosorption, and degradation products that can protect and promote the regeneration of nerve cells was selected to combine with galantamine, a natural representative cholinesterase inhibitor, to develop a new nano drug delivery system for nasal delivery of anti-Alzheimer's disease with a multi-target synergistic effect. Synchronous analysis was conducted on the blood and brain tissue drug concentrations after intravenous and nasal administration of the original drug solution and system solution. The brain targeting index (DTI) is used to evaluate the brain targeting effect of the nano-drug delivery system after intranasal administration. RESULTS: The blood concentration of galantamine original drug solution and galantamine system solution after intravenous injection and nasal show that in the two administration methods of intravenous injection and nasal administration, under the same administration method, the time point of the system reaching the highest blood drug concentration is much higher than that of the original drug. The content of galantamine in plasma samples and tissue samples indicate that after intravenous administration and intranasal administration of the galantamine system, at the same time point, the drug concentration in brain tissue was far greater than that of the original drug of galantamine, and the duration was also longer. The concentration of drugs in brain tissue decreased gradually in the order of olfactory bulb, olfactory tract, brain, and cerebellum. In the brain tissues of the olfactory bulb, olfactory tract, cerebrum, and cerebellum, the drug concentration of the galantamine system after intravenous injection is lower than that after nasal administration. CONCLUSIONS: This study concludes that compared with the original drug solution, the nano drug delivery system has significant brain targeting for nasal administration, and intravenous injection also has brain targeting. In the olfactory bulb, olfactory tract, brain, and cerebellum, the brain targeting index at the olfactory bulb is the highest, and the targeting is the best.
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Administración Intranasal , Enfermedad de Alzheimer , Encéfalo , Quitosano , Inhibidores de la Colinesterasa , Sistemas de Liberación de Medicamentos , Galantamina , Enfermedad de Alzheimer/tratamiento farmacológico , Quitosano/química , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Animales , Galantamina/administración & dosificación , Galantamina/farmacocinética , Inhibidores de la Colinesterasa/administración & dosificación , Humanos , Ratas , Masculino , Sistema de Administración de Fármacos con Nanopartículas/químicaRESUMEN
BACKGROUND: The oral administration of drugs for treating ulcerative colitis (UC) is hindered by several factors, including inadequate gastrointestinal stability, insufficient accumulation in colonic lesions, and uncontrolled drug release. METHODS: A multiple sensitive nano-delivery system comprising ß-cyclodextrin (CD) and 4-(hydroxymethyl)phenylboronic acid (PAPE) with enzyme/reactive oxygen species (ROS) sensitivity was developed to load celastrol (Cel) as a comprehensive treatment for UC. RESULTS: Owing to the positive charge in the site of inflamed colonic mucosa, the negatively charged nanomedicine (Cel/NPs) could efficiently accumulate. Expectedly, Cel/NPs showed excellent localization ability to colon in vitro and in vivo tests. The elevated concentration of ROS and intestinal enzymes in the colon microenvironment quickly break the CD, resulting in Cel release partially to rebalance microbiota and recover the intestinal barrier. The accompanying cellular internalization of residual Cel/NPs, along with the high concentration of cellular ROS to trigger Cel burst release, could decrease the expression of inflammatory cytokines, inhibit colonic cell apoptosis, promote the macrophage polarization, scavenge ROS, and regulate the TLR4/NF-κB signaling pathway, which certified that Cel/NPs possessed a notably anti-UC therapy outcome. CONCLUSIONS: We provide a promising strategy for addressing UC symptoms via an enzyme/ROS-sensitive oral platform capable of releasing drugs on demand.
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Colitis Ulcerosa , Triterpenos Pentacíclicos , Especies Reactivas de Oxígeno , Colitis Ulcerosa/tratamiento farmacológico , Triterpenos Pentacíclicos/farmacología , Triterpenos Pentacíclicos/uso terapéutico , Animales , Especies Reactivas de Oxígeno/metabolismo , Ratones , Humanos , Nanopartículas/química , beta-Ciclodextrinas/química , Masculino , Células RAW 264.7 , Inflamación/tratamiento farmacológico , Microbioma Gastrointestinal/efectos de los fármacos , Colon/metabolismo , Colon/efectos de los fármacos , Liberación de Fármacos , Ratones Endogámicos C57BL , Triterpenos/farmacología , Triterpenos/química , Sistema de Administración de Fármacos con Nanopartículas/química , Mucosa Intestinal/metabolismoRESUMEN
Active targeting to cancer involves exploiting specific interactions between receptors on the surface of cancer cells and targeting moieties conjugated to the surface of vectors such that site-specific delivery is achieved. Prostate specific membrane antigen (PSMA) has proved to be an excellent target for active targeting to prostate cancer. We report the synthesis and use of a PSMA-specific ligand (Glu-NH-CO-NH-Lys) for the site-specific delivery of brusatol- and docetaxel-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles to prostate cancer. The PSMA targeting ligand covalently linked to PLGA-PEG3400 was blended with methoxyPEG-PLGA to prepare brusatol- and docetaxel-loaded nanoparticles with different surface densities of the targeting ligand. Flow cytometry was used to evaluate the impact of different surface densities of the PSMA targeting ligand in LNCaP prostate cancer cells at 15â¯min and 2â¯h. Cytotoxicity evaluations of the targeted nanoparticles reveal differences based on PSMA expression in PC-3 and LNCaP cells. In addition, levels of reactive oxygen species (ROS) were measured using the fluorescent indicator, H2DCFDA, by flow cytometry. PSMA-targeted nanoparticles loaded with docetaxel and brusatol showed increased ROS generation in LNCaP cells compared to PC-3 at different time points. Furthermore, the targeted nanoparticles were evaluated in male athymic BALB/c mice implanted with PSMA-producing LNCaP cell tumors. Evaluation of the percent relative tumor volume show that brusatol-containing nanoparticles show great promise in inhibiting tumor growth. Our data also suggest that the dual drug-loaded targeted nanoparticle platform improves the efficacy of docetaxel in male athymic BALB/c mice implanted with PSMA-producing LNCaP cell tumors.
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Antígenos de Superficie , Docetaxel , Glutamato Carboxipeptidasa II , Nanopartículas , Neoplasias de la Próstata , Masculino , Docetaxel/farmacología , Docetaxel/administración & dosificación , Animales , Humanos , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Glutamato Carboxipeptidasa II/metabolismo , Antígenos de Superficie/metabolismo , Línea Celular Tumoral , Nanopartículas/química , Especies Reactivas de Oxígeno/metabolismo , Células PC-3 , Ratones , Ensayos Antitumor por Modelo de Xenoinjerto , Pez Cebra , Ratones Desnudos , Antineoplásicos/farmacología , Antineoplásicos/administración & dosificación , Ratones Endogámicos BALB C , Sistema de Administración de Fármacos con Nanopartículas/químicaRESUMEN
The coronavirus (COVID-19) pandemic has underscored the critical role of mRNA-based vaccines as powerful, adaptable, readily manufacturable, and safe methodologies for prophylaxis. mRNA-based treatments are emerging as a hopeful avenue for a plethora of conditions, encompassing infectious diseases, cancer, autoimmune diseases, genetic diseases, and rare disorders. Nonetheless, the in vivo delivery of mRNA faces challenges due to its instability, suboptimal delivery, and potential for triggering undesired immune reactions. In this context, the development of effective drug delivery systems, particularly nanoparticles (NPs), is paramount. Tailored with biophysical and chemical properties and susceptible to surface customization, these NPs have demonstrated enhanced mRNA delivery in vivo and led to the approval of several NPs-based formulations for clinical use. Despite these advancements, the necessity for developing a refined, targeted NP delivery system remains imperative. This review comprehensively surveys the biological, translational, and clinical progress in NPs-mediated mRNA therapeutics for both the prevention and treatment of diverse diseases. By addressing critical factors for enhancing existing methodologies, it aims to inform the future development of precise and efficacious mRNA-based therapeutic interventions.
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COVID-19 , Sistema de Administración de Fármacos con Nanopartículas , ARN Mensajero , Humanos , ARN Mensajero/genética , ARN Mensajero/administración & dosificación , Sistema de Administración de Fármacos con Nanopartículas/química , COVID-19/prevención & control , Nanopartículas/química , Sistemas de Liberación de Medicamentos/métodos , Animales , SARS-CoV-2/efectos de los fármacos , Vacunas de ARNmRESUMEN
Central nervous system (CNS) diseases, ranging from brain cancers to neurodegenerative disorders like dementia and acute conditions such as strokes, have been heavily burdening healthcare and have a direct impact on patient quality of life. A significant hurdle in developing effective treatments is the presence of the blood-brain barrier (BBB), a highly selective barrier that prevents most drugs from reaching the brain. The tight junctions and adherens junctions between the endothelial cells and various receptors expressed on the cells make the BBB form a nonfenestrated and highly selective structure that is crucial for brain homeostasis but complicates drug delivery. Nanotechnology offers a novel pathway to circumvent this barrier, with nanoparticles engineered to ferry drugs across the BBB, protect drugs from degradation, and deliver medications to the designated area. After years of development, nanoparticle optimization, including sizes, shapes, surface modifications, and targeting ligands, can enable nanomaterials tailored to specific brain drug delivery settings. Moreover, smart nano drug delivery systems can respond to endogenous and exogenous stimuli that control subsequent drug release. Here, we address the importance of the BBB in brain disease treatment, summarize different delivery routes for brain drug delivery, discuss the cutting-edge nanotechnology-based strategies for brain drug delivery, and further offer valuable insights into how these innovations in nanoparticle technology could revolutionize the treatment of CNS diseases, presenting a promising avenue for noninvasive, targeted therapeutic interventions.
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Barrera Hematoencefálica , Encefalopatías , Sistemas de Liberación de Medicamentos , Nanopartículas , Nanotecnología , Humanos , Barrera Hematoencefálica/metabolismo , Sistemas de Liberación de Medicamentos/métodos , Encefalopatías/tratamiento farmacológico , Nanotecnología/métodos , Nanopartículas/química , Animales , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Sistema de Administración de Fármacos con Nanopartículas/químicaRESUMEN
Doxorubicin (DOX) is a chemotherapy drug used for hepatocellular carcinoma (HCC) treatment, but its effectiveness can be dramatically dampened by cancer cell chemoresistance. Signal transducer and activator of transcription 3 (STAT3) is implicated with drug resistance in a range of cancers (e.g., HCC), and the STAT3 inhibition can reverse the resistance of cancer cells to chemotherapeutic drugs. In the present study, a combination regimen to improve the efficiency of DOX was provided via the STAT3 blockade using plumbagin (PLB). A poly(lactic-co-glycolic acid) decorated by polyethylene glycol and aminoethyl anisamide was produced in the present study with the hope of generating the nanoparticles for co-delivery of DOX and PLB. The resulting co-formulation suppressed the STAT3 activity and achieved the synergistic chemotherapy, which led to tumor inhibition in the mice with subcutaneous DOX-resistant HCC, without causing any toxicity. The present study reveals the synergism of DOX and PLB, and demonstrates a promising combinatorial approach for treating HCC.
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Carcinoma Hepatocelular , Doxorrubicina , Sinergismo Farmacológico , Neoplasias Hepáticas , Naftoquinonas , Doxorrubicina/administración & dosificación , Doxorrubicina/farmacología , Doxorrubicina/química , Naftoquinonas/administración & dosificación , Naftoquinonas/química , Naftoquinonas/farmacología , Animales , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Humanos , Polietilenglicoles/química , Polietilenglicoles/administración & dosificación , Ratones Endogámicos BALB C , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/antagonistas & inhibidores , Línea Celular Tumoral , Ratones , Nanopartículas/química , Resistencia a Antineoplásicos/efectos de los fármacos , Sistema de Administración de Fármacos con Nanopartículas/química , Ratones Desnudos , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/farmacología , Masculino , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologíaRESUMEN
In recent years, the use of arsenic trioxide (ATO) in the context of ovarian cancer chemotherapy has attracted significant attention. However, ATO's limited biocompatibility and the occurrence of severe toxic side effects hinder its clinical application. A nanoparticle (NP) drug delivery system using ATO as a therapeutic agent is reported in this study. Achieving a synergistic effect by combining starvation therapy, chemodynamic therapy, and chemotherapy for the treatment of ovarian cancer was the ultimate goal of this system. This nanotechnology-based drug delivery system (NDDS) introduced arsenic-manganese complexes into cancer cells, leading to the subsequent release of lethal arsenic ions (As3+) and manganese ions (Mn2+). The acidic microenvironment of the tumor facilitated this process, and MR imaging offered real-time monitoring of the ATO dose distribution. Simultaneously, to produce reactive oxygen species that induced cell death through a Fenton-like reaction, Mn2+ exploited the surplus of hydrogen peroxide (H2O2) within tumor cells. Glucose oxidase-based starvation therapy further supported this mechanism, which restored H2O2 and lowered the cellular acidity. Consequently, this approach achieved self-enhanced chemodynamic therapy. Homologous targeting of the NPs was facilitated through the use of SKOV3 cell membranes that encapsulated the NPs. Hence, the use of a multimodal NDDS that integrated ATO delivery, therapy, and monitoring exhibited superior efficacy and biocompatibility compared with the nonspecific administration of ATO. This approach presents a novel concept for the diagnosis and treatment of ovarian cancer.
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Antineoplásicos , Trióxido de Arsénico , Nanopartículas , Neoplasias Ováricas , Femenino , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Humanos , Concentración de Iones de Hidrógeno , Línea Celular Tumoral , Trióxido de Arsénico/administración & dosificación , Trióxido de Arsénico/química , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Antineoplásicos/farmacología , Nanopartículas/química , Manganeso/química , Manganeso/administración & dosificación , Peróxido de Hidrógeno , Especies Reactivas de Oxígeno/metabolismo , Ratones , Materiales Biomiméticos/química , Materiales Biomiméticos/administración & dosificación , Ratones Desnudos , Sistemas de Liberación de Medicamentos/métodos , Sistema de Administración de Fármacos con Nanopartículas/química , Glucosa Oxidasa/administración & dosificación , Ratones Endogámicos BALB CRESUMEN
Liver fibrosis (LF) is a pathological repair reaction caused by a chronic liver injury that affects the health of millions of people worldwide, progressing to life-threatening cirrhosis and liver cancer without timely intervention. Due to the complexity of LF pathology, multiple etiological characteristics, and the deposited extracellular matrix, traditional drugs cannot reach appropriate targets in a time-space matching way, thus decreasing the therapeutic effect. Nanoparticle drug delivery systems (NDDS) enable multidrug co-therapy and develop multifactor delivery strategies targeting pathological processes, showing great potential in LF therapy. Based on the pathogenesis and the current clinical treatment status of LF, we systematically elucidate the targeting mechanism of NDDS used in the treatment of LF. Subsequently, we focus on the progress of drug delivery applications for LF, including combined delivery for the liver fibrotic pathological environment, overcoming biological barriers, precise intracellular regulation, and intelligent responsive delivery for the liver fibrotic microenvironment. We hope that this review will inspire the rational design of NDDS for LF in the future in order to provide ideas and methods for promoting LF regression and cure.
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Cirrosis Hepática , Humanos , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/patología , Animales , Sistema de Administración de Fármacos con Nanopartículas/química , Sistemas de Liberación de Medicamentos , Nanopartículas/químicaRESUMEN
Inflammatory bowel disease (IBD) is a chronic, non-specific inflammatory condition characterized by recurring inflammation of the intestinal mucosa. However, the existing IBD treatments are ineffective and have serious side effects. The etiology of IBD is multifactorial and encompasses immune, genetic, environmental, dietary, and microbial factors. The nanoparticles (NPs) developed based on specific targeting methodologies exhibit great potential as nanotechnology advances. Nanoparticles are defined as particles between 1 and 100 nm in size. Depending on their size and surface functionality, NPs exhibit different properties. A variety of nanoparticle types have been employed as drug carriers for the treatment of inflammatory bowel disease (IBD), with encouraging outcomes observed in experimental models. They increase the bioavailability of drugs and enable targeted drug delivery, promoting localized treatment and thus enhancing efficacy. Nevertheless, numerous challenges persist in the translation from nanomedicine to clinical application, including enhanced formulations and preparation techniques, enhanced drug safety profiles, and so forth. In the future, it will be necessary for scientists and clinicians to collaborate in order to study disease mechanisms, develop new drug delivery strategies, and screen new nanomedicines. Nevertheless, numerous challenges persist in the translation from nanomedicine to clinical application, including enhanced formulations and preparation techniques, enhanced drug safety profiles, and so forth. In the future, it will be necessary for scientists and clinicians to collaborate in order to study disease mechanisms, develop new drug delivery strategies, and screen new nanomedicines.
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Sistemas de Liberación de Medicamentos , Enfermedades Inflamatorias del Intestino , Nanopartículas , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Nanopartículas/química , Animales , Portadores de Fármacos/química , Sistema de Administración de Fármacos con Nanopartículas/química , NanomedicinaRESUMEN
Purpose: The purpose of this study is to address the high mortality and poor prognosis associated with Acute Respiratory Distress Syndrome (ARDS), conditions characterized by acute and progressive respiratory failure. The primary goal was to prolong drug circulation time, increase drug accumulation in the lungs, and minimize drug-related side effects. Methods: Simvastatin (SIM) was used as the model drug in this study. Employing a red blood cell surface-loaded nanoparticle drug delivery technique, pH-responsive cationic nanoparticles loaded with SIM were non-covalently adsorbed onto the surface of red blood cells (RBC), creating a novel drug delivery system (RBC@SIM-PEI-PPNPs). Results: The RBC@SIM-PEI-PPNPs delivery system effectively extended the drug's circulation time, providing an extended therapeutic window. Additionally, this method substantially improved the targeted accumulation of SIM in lung tissues, thereby enhancing the drug's efficacy in treating ARDS and impeding its progression to ARDS. Crucially, the system showed a reduced risk of adverse drug reactions. Conclusion: RBC@SIM-PEI-PPNPs demonstrates promise in ARDS and ARDS treatment. This innovative approach successfully overcomes the limitations associated with SIM's poor solubility and low bioavailability, resulting in improved therapeutic outcomes and fewer drug-related side effects. This research holds significant clinical implications and highlights its potential for broader application in drug delivery and lung disease treatment.
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Eritrocitos , Síndrome de Dificultad Respiratoria , Simvastatina , Simvastatina/administración & dosificación , Simvastatina/farmacocinética , Simvastatina/química , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , Eritrocitos/efectos de los fármacos , Animales , Pulmón/efectos de los fármacos , Humanos , Masculino , Sistema de Administración de Fármacos con Nanopartículas/química , Sistema de Administración de Fármacos con Nanopartículas/farmacocinética , Nanopartículas/química , Nanopartículas/administración & dosificación , Ratones , Polietileneimina/química , Sistemas de Liberación de Medicamentos/métodos , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinéticaRESUMEN
Background and Purpose: Natural products are potential sources of anticancer components. Among various species, the lipophilic extract of the Viscum album subsp. austriacum (Wiesb.) Vollm. (VALE) has shown promising therapeutic potential. The present work aimed to qualify the plant source and characterize the extract's chemical profile. In addition, a self-nanoemulsifying drug delivery system (SNEDDS) containing VALE (SNEDDS-VALE) was developed. Methods: V. album subsp. austriacum histochemistry was performed, and the chemical profile of VALE was analyzed by GC-MS. After the SNEEDS-VALE development, its morphology was visualized by transmission electron microscopy (TEM), while its stability was evaluated by the average droplet size, polydispersity index (PdI) and pH. Lastly, SNEDDS-VALE chemical stability was evaluated by LC-DAD-MS. Results: The histochemical analysis showed the presence of lipophilic compounds in the leaves and stems. The major compound in the VALE was oleanolic acid, followed by lupeol acetate and ursolic acid. SNEDDS was composed of medium chain triglyceride and Kolliphor® RH 40 (PEG-40 hydrogenated castor oil). A homogeneous, isotropic and stable nanoemulsion was obtained, with an average size of 36.87 ± 1.04 nm and PdI of 0.14 ± 0.02, for 14 weeks. Conclusion: This is the first histochemistry analysis of V. album subsp. austriacum growing on Pinus sylvestris L. which provided detailed information regarding its lipophilic compounds. A homogeneous, isotropic and stable SNEDDS-VALE was obtained to improve the low water solubility of VALE. Further, in vitro and in vivo experiments should be performed, in order to evaluate the antitumoral potential of SNEDDS-VALE.
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Emulsiones , Extractos Vegetales , Viscum album , Extractos Vegetales/química , Extractos Vegetales/administración & dosificación , Viscum album/química , Emulsiones/química , Hojas de la Planta/química , Sistemas de Liberación de Medicamentos/métodos , Tamaño de la Partícula , Sistema de Administración de Fármacos con Nanopartículas/química , Nanopartículas/químicaRESUMEN
Lenvatinib (LVN) is a potentially effective multiple-targeted receptor tyrosine kinase inhibitor approved for treating hepatocellular carcinoma, metastatic renal cell carcinoma and thyroid cancer. Nonetheless, poor pharmacokinetic properties including poor water solubility and rapid metabolic, complex tumor microenvironment, and drug resistance have impeded its satisfactory therapeutic efficacy. This article comprehensively reviews the uses of nanotechnology in LVN to improve antitumor effects. With the characteristic of high modifiability and loading capacity of the nano-drug delivery system, an active targeting approach, controllable drug release, and biomimetic strategies have been devised to deliver LVN to target tumors in sequence, compensating for the lack of passive targeting. The existing applications and advances of LVN in improving therapeutic efficacy include improving longer-term efficiency, achieving higher efficiency, combination therapy, tracking and diagnosing application and reducing toxicity. Therefore, using multiple strategies combined with photothermal, photodynamic, and immunoregulatory therapies potentially overcomes multi-drug resistance, regulates unfavorable tumor microenvironment, and yields higher synergistic antitumor effects. In brief, the nano-LVN delivery system has brought light to the war against cancer while at the same time improving the antitumor effect. More intelligent and multifunctional nanoparticles should be investigated and further converted into clinical applications in the future.
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Antineoplásicos , Sistema de Administración de Fármacos con Nanopartículas , Compuestos de Fenilurea , Quinolinas , Humanos , Quinolinas/química , Quinolinas/farmacocinética , Quinolinas/administración & dosificación , Quinolinas/farmacología , Compuestos de Fenilurea/química , Compuestos de Fenilurea/farmacocinética , Compuestos de Fenilurea/administración & dosificación , Antineoplásicos/química , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Antineoplásicos/farmacocinética , Sistema de Administración de Fármacos con Nanopartículas/química , Animales , Microambiente Tumoral/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Nanopartículas/químicaRESUMEN
Background: Vitamin E, which is also known as tocopherol, is a compound with a polyphenol structure. Its esterified derivative, Vitamin E succinate (VES), exhibits unique anticancer and healthcare functions as well as immunomodulatory effects. Natural polysaccharides are proved to be a promising material for nano-drug delivery systems, which show excellent biodegradability and biocompatibility. In this study, we employed a novel bletilla striata polysaccharide-vitamin E succinate polymer (BSP-VES) micelles to enhance the tumor targeting and anti-colon cancer effect of andrographolide (AG). Methods: BSP-VES polymer was synthesized through esterification and its structure was confirmed using 1H NMR. AG@BSP-VES was prepared via the dialysis method and the drug loading, entrapment efficiency, stability, and safety were assessed. Furthermore, the tumor targeting ability of AG@BSP-VES was evaluated through targeted cell uptake and in vivo imaging. The antitumor activity of AG@BSP-VES was measured in vitro using MTT assay, Live&Dead cell staining, and cell scratch test. Results: In this study, we successfully loaded AG into BSP-VES micelles (AG@BSP-VES), which exhibited good stability, biosafety and sustained release effect. In addition, AG@BSP-VES also showed excellent internalization capability into CT26 cells compared with NCM460 cells in vitro. Meanwhile, the specific delivery of AG@BSP-VES micelles into subcutaneous and in-situ colon tumors was observed compared with normal colon tissues in vivo during the whole experiment process (1-24 h). What's more, AG@BSP-VES micelles exhibited significant antitumor activities than BSP-VES micelles and free AG. Conclusion: The study provides a meaningful new idea and method for application in drug delivery system and targeted treatment of colon cancer based on natural polysaccharides.