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1.
Int J Nanomedicine ; 19: 4377-4409, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38774029

RESUMEN

Angiogenesis, or the formation of new blood vessels, is a natural defensive mechanism that aids in the restoration of oxygen and nutrition delivery to injured brain tissue after an ischemic stroke. Angiogenesis, by increasing vessel development, may maintain brain perfusion, enabling neuronal survival, brain plasticity, and neurologic recovery. Induction of angiogenesis and the formation of new vessels aid in neurorepair processes such as neurogenesis and synaptogenesis. Advanced nano drug delivery systems hold promise for treatment stroke by facilitating efficient transportation across the the blood-brain barrier and maintaining optimal drug concentrations. Nanoparticle has recently been shown to greatly boost angiogenesis and decrease vascular permeability, as well as improve neuroplasticity and neurological recovery after ischemic stroke. We describe current breakthroughs in the development of nanoparticle-based treatments for better angiogenesis therapy for ischemic stroke employing polymeric nanoparticles, liposomes, inorganic nanoparticles, and biomimetic nanoparticles in this study. We outline new nanoparticles in detail, review the hurdles and strategies for conveying nanoparticle to lesions, and demonstrate the most recent advances in nanoparticle in angiogenesis for stroke treatment.


Asunto(s)
Accidente Cerebrovascular Isquémico , Nanopartículas , Neovascularización Fisiológica , Humanos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Animales , Nanopartículas/química , Neovascularización Fisiológica/efectos de los fármacos , Barrera Hematoencefálica/efectos de los fármacos , Liposomas/química , Sistemas de Liberación de Medicamentos/métodos , Sistema de Administración de Fármacos con Nanopartículas/química , Angiogénesis
2.
Yakugaku Zasshi ; 144(5): 511-519, 2024.
Artículo en Japonés | MEDLINE | ID: mdl-38692926

RESUMEN

Nanoparticles, including liposomes and lipid nanoparticles, have garnered global attention due to their potential applications in pharmaceuticals, vaccines, and gene therapies. These particles enable targeted delivery of new drug modalities such as highly active small molecules and nucleic acids. However, for widespread use of nanoparticle-based formulations, it is crucial to comprehensively analyze their characteristics to ensure both efficacy and safety, as well as enable consistent production. In this context, this review focuses on our research using atomic force microscopy (AFM) to study liposomes and lipid nanoparticles. Our work significantly contributes to the capability of AFM to measure various types of liposomes in an aqueous medium, providing valuable insights into the mechanical properties of these nanoparticles. We discuss the applications of this AFM technique in assessing the quality of nanoparticle-based pharmaceuticals and developing membrane-active peptides.


Asunto(s)
Liposomas , Microscopía de Fuerza Atómica , Nanopartículas , Microscopía de Fuerza Atómica/métodos , Lípidos/química , Sistemas de Liberación de Medicamentos , Sistema de Administración de Fármacos con Nanopartículas/química , Péptidos/química
3.
Int J Nanomedicine ; 19: 4021-4040, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38736657

RESUMEN

Cataract is a leading cause of blindness globally, and its surgical treatment poses a significant burden on global healthcare. Pharmacologic therapies, including antioxidants and protein aggregation reversal agents, have attracted great attention in the treatment of cataracts in recent years. Due to the anatomical and physiological barriers of the eye, the effectiveness of traditional eye drops for delivering drugs topically to the lens is hindered. The advancements in nanomedicine present novel and promising strategies for addressing challenges in drug delivery to the lens, including the development of nanoparticle formulations that can improve drug penetration into the anterior segment and enable sustained release of medications. This review introduces various cutting-edge drug delivery systems for cataract treatment, highlighting their physicochemical properties and surface engineering for optimal design, thus providing impetus for further innovative research and potential clinical applications of anti-cataract drugs.


Asunto(s)
Catarata , Sistemas de Liberación de Medicamentos , Nanomedicina , Humanos , Catarata/tratamiento farmacológico , Nanomedicina/métodos , Sistemas de Liberación de Medicamentos/métodos , Nanopartículas/química , Animales , Cristalino/efectos de los fármacos , Extracción de Catarata , Sistema de Administración de Fármacos con Nanopartículas/química , Soluciones Oftálmicas/química , Soluciones Oftálmicas/farmacocinética , Soluciones Oftálmicas/administración & dosificación
4.
Mikrochim Acta ; 191(6): 326, 2024 05 13.
Artículo en Inglés | MEDLINE | ID: mdl-38740583

RESUMEN

Migration is an initial step in tumor expansion and metastasis; suppressing cellular migration is beneficial to cancer therapy. Herein, we designed a novel biogated nanoagents that integrated the migration inhibitory factor into the mesoporous silica nanoparticle (MSN) drug delivery nanosystem to realize cell migratory inhibition and synergistic treatment. Antisense oligonucleotides (Anti) of microRNA-330-3p, which is positively related with cancer cell proliferation, migration, invasion, and angiogenesis, not only acted as the locker for blocking drugs but also acted as the inhibitory factor for suppressing migration via gene therapy. Synergistic with gene therapy, the biogated nanoagents (termed as MSNs-Gef-Anti) could achieve on-demand drug release based on the intracellular stimulus-recognition and effectively kill tumor cells. Experimental results synchronously demonstrated that the migration suppression ability of MSNs-Gef-Anti nanoagents (nearly 30%) significantly contributed to cancer therapy, and the lethality rate of the non-small-cell lung cancer was up to 70%. This strategy opens avenues for realizing efficacious cancer therapy and should provide an innovative way for pursuing the rational design of advanced nano-therapeutic platforms with the combination of cancer cell migratory inhibition.


Asunto(s)
Movimiento Celular , Quimioterapia Combinada , Nanopartículas , Neoplasias , Dióxido de Silicio , Movimiento Celular/efectos de los fármacos , Dióxido de Silicio/química , Quimioterapia Combinada/métodos , Neoplasias/tratamiento farmacológico , Sistema de Administración de Fármacos con Nanopartículas/química , Sistema de Administración de Fármacos con Nanopartículas/uso terapéutico , Nanopartículas/química , Nanopartículas/uso terapéutico , Nanopartículas/ultraestructura , Células A549 , Microscopía Electrónica de Transmisión , Humanos
5.
Eur J Pharm Biopharm ; 199: 114310, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38705311

RESUMEN

Nanoparticle-based drug delivery systems hold potential in chemotherapy, but their limited accumulation in tumor tissues hinders effective drug concentration for combating tumor growth. Hence, altering the physicochemical properties of nanoparticles, particularly their surface charge, can enhance their performance. This study utilized a computational model to explore a nanoparticle drug delivery system capable of dynamically adjusting its surface charge. In the model, nanoparticles in the bloodstream were assigned a neutral or positive charge, which, upon reaching the tumor microenvironment, switched to a neutral or negative charge, and releasing chemotherapy drugs into the extracellular space. Results revealed that circulating nanoparticles with a positive surface charge, despite having a shorter circulation and high clearance rate compared to their neutral counterparts, could accumulate significantly in the tissue due to their high transvascular rate. After extravasation, neutralized surface-charged nanoparticles tended to accumulate only near blood microvessels due to their low diffusion rate, resulting in substantial released drug drainage back into the bloodstream. On the other hand, nanoparticles with a negative surface charge in the tumor's extracellular space, due to the reduction of nano-bio interactions, were able to penetrate deeper into the tumor, and increasing drug bioavailability by reducing the volume of drained drugs. Furthermore, the analysis suggested that burst drug release yields a higher drug concentration than sustained drug release, however their creation of bioavailability dependent on nanoparticle accumulation in the tissue. The study's findings demonstrate the potential of this delivery system and offer valuable insights for future research in this area.


Asunto(s)
Antineoplásicos , Nanopartículas , Neoplasias , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacocinética , Humanos , Microambiente Tumoral/efectos de los fármacos , Sistemas de Liberación de Medicamentos/métodos , Disponibilidad Biológica , Liberación de Fármacos , Sistema de Administración de Fármacos con Nanopartículas/química , Simulación por Computador , Distribución Tisular , Portadores de Fármacos/química
6.
Drug Des Devel Ther ; 18: 1007-1022, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38567254

RESUMEN

Low back pain (LBP) is a common condition that has substantial consequences on individuals and society, both socially and economically. The primary contributor to LBP is often identified as intervertebral disc degeneration (IVDD), which worsens and leads to significant spinal problems. The conventional treatment approach for IVDD involves physiotherapy, drug therapy for pain management, and, in severe cases, surgery. However, none of these treatments address the underlying cause of the condition, meaning that they cannot fundamentally reverse IVDD or restore the mechanical function of the spine. Nanotechnology and regenerative medicine have made significant advancements in the field of healthcare, particularly in the area of nanodrug delivery systems (NDDSs). These approaches have demonstrated significant potential in enhancing the efficacy of IVDD treatments by providing benefits such as high biocompatibility, biodegradability, precise drug delivery to targeted areas, prolonged drug release, and improved therapeutic results. The advancements in different NDDSs designed for delivering various genes, cells, proteins and therapeutic drugs have opened up new opportunities for effectively addressing IVDD. This comprehensive review provides a consolidated overview of the recent advancements in the use of NDDSs for the treatment of IVDD. It emphasizes the potential of these systems in overcoming the challenges associated with this condition. Meanwhile, the insights and ideas presented in this review aim to contribute to the advancement of precise IVDD treatment using NDDSs.


Asunto(s)
Degeneración del Disco Intervertebral , Dolor de la Región Lumbar , Humanos , Degeneración del Disco Intervertebral/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Manejo del Dolor , Liberación de Fármacos , Sistema de Administración de Fármacos con Nanopartículas
7.
Sci Rep ; 14(1): 8567, 2024 04 12.
Artículo en Inglés | MEDLINE | ID: mdl-38609391

RESUMEN

A novel pH/redox-responsive hyperbranched MeO-PEG-b-(NIPAAm-co-PBAE) nanoparticles (NPs) were designed with size shrinkage and charge-reversible potential for targeted delivery of docetaxel (DTX) to MDA-MB-231 cell lines. In the tumor microenvironment (TME), amine protonation induces charge reversal and disulfide bond cleavage under high TME GSH concentration causing size shrinkage, improved deep tumor penetration, and active targeting of the therapeutic agents. These nano drug delivery systems (NDDSs) significantly promoted cancer cell uptake (~ 100% at 0.5 h), facilitating site-specific delivery and deep tumor penetration. The MTT assay revealed significantly higher cytotoxicity (P value < 0.0001) for DTX-loaded NPs compared to free DTX. Cell cycle analysis revealed G2/M (58.3 ± 2.1%) and S (21.5 ± 1.3%) arrest for DTX-loaded NPs, while free DTX caused G2/M (67.9 ± 1.1%) and sub-G1 (10.3 ± 0.8%) arrest. DTX-loaded NPs induced higher apoptosis (P value < 0.001) in MDA-MB-231 cells (71.5 ± 2.8%) compared to free DTX (42.3 ± 3.1%). Western blotting and RT-PCR assays confirmed significant up-regulation of protein levels and apoptotic genes by DTX-loaded NPs compared to free DTX. In conclusion, TME-responsive charge reversal and size-shrinkable smart NDDSs designed based on low pH, and high glutathione (GSH), offer more effective site-specific delivery of therapeutic agents to tumors.


Asunto(s)
Neoplasias , Microambiente Tumoral , Humanos , Docetaxel/farmacología , Glutatión , Sistema de Administración de Fármacos con Nanopartículas , Oxidación-Reducción , Polímeros , Concentración de Iones de Hidrógeno
8.
Biomed Pharmacother ; 174: 116541, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38565063

RESUMEN

BACKGROUND: Hypertension, a highly prevalent chronic disease, is known to inflict severe damage upon blood vessels. In our previous study, isoliensinine, a kind of bibenzyl isoquinoline alkaloid which isolated from a TCM named Lotus Plumule (Nelumbo nucifera Gaertn), exhibits antihypertensive and vascular smooth muscle proliferation-inhibiting effects, but its application is limited due to poor water solubility and low bioavailability. In this study, we proposed to prepare isoliensinine loaded by PEG-PLGA polymer nanoparticles to increase its efficacy METHOD: We synthesized and thoroughly characterized PEG-PLGA nanoparticles loaded with isoliensinine using a nanoprecipitation method, denoted as, PEG-PLGA@Isoliensinine. Additionally, we conducted comprehensive investigations into the stability of PEG-PLGA@Isoliensinine, in vitro drug release profiles, and in vivo pharmacokinetics. Furthermore, we assessed the antihypertensive efficacy of this nano-system through in vitro experiments on A7R5 cells and in vivo studies using AngII-induced mice. RESULT: The findings reveal that PEG-PLGA@Isoliensinine significantly improves isoliensinine absorption by A7R5 cells and enhances targeted in vivo distribution. This translates to a more effective reduction of AngII-induced hypertension and vascular smooth muscle proliferation. CONCLUSION: In this study, we successfully prepared PEG-PLGA@Isoliensinine by nano-precipitation, and we confirmed that PEG-PLGA@Isoliensinine surpasses free isoliensinine in its effectiveness for the treatment of hypertension, as demonstrated through both in vivo and in vitro experiments. SIGNIFICANCE: This study lays the foundation for isoliensinine's clinical use in hypertension treatment and vascular lesion protection, offering new insights for enhancing the bioavailability of traditional Chinese medicine components. Importantly, no toxicity was observed, affirming the successful implementation of this innovative drug delivery system in vivo and offers a promising strategy for enhancing the effectiveness of Isoliensinine and propose an innovative avenue for developing novel formulations of traditional Chinese medicine monomers.


Asunto(s)
Antihipertensivos , Liberación de Fármacos , Hipertensión , Isoquinolinas , Polietilenglicoles , Animales , Hipertensión/tratamiento farmacológico , Polietilenglicoles/química , Antihipertensivos/administración & dosificación , Antihipertensivos/farmacología , Antihipertensivos/química , Antihipertensivos/farmacocinética , Masculino , Isoquinolinas/farmacología , Isoquinolinas/administración & dosificación , Isoquinolinas/química , Isoquinolinas/farmacocinética , Ratas , Ratones , Nanopartículas/química , Línea Celular , Sistema de Administración de Fármacos con Nanopartículas/química , Ratas Sprague-Dawley , Portadores de Fármacos/química , Presión Sanguínea/efectos de los fármacos , Poliésteres/química
9.
J Cancer Res Ther ; 20(2): 684-694, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38687941

RESUMEN

OBJECTIVES: Gypenoside (Gyp) is easily degraded in the gastrointestinal tract, resulting in its low bioavailability. We aimed to develop a tumor-targeted Gyp nanodrug delivery system and to investigate its antitumor effect in vitro. MATERIALS AND METHODS: We used Gyp as the therapeutic drug molecule, mesoporous silica (MSN) and liposome (Lipo) as the drug carrier and protective layers, and aptamer SYL3C as the targeting element to establish a tumor-targeted nanodrug delivery system (i.e., SYL3C-Lipo@Gyp-MSN). The characteristics of SYL3C-Lipo@Gyp-MSN were investigated, and its drug release performance, cell uptake, and antitumor activity in vitro were evaluated. RESULTS: A tumor-targeted Gyp nanodrug delivery system was successfully prepared. The SYL3C-Lipo@Gyp-MSN was spherical or ellipsoidal; had good dispersion, which enabled it to specifically target and kill the liver tumor cell HepG2; and effectively protected the early leakage of Gyp. CONCLUSIONS: We have established a tumor-targeted nanodrug delivery system that can target and kill liver cancer cells and may provide a strategy for preparing new nanodrug-loaded preparations of traditional Chinese medicine.


Asunto(s)
Gynostemma , Liposomas , Humanos , Gynostemma/química , Liposomas/química , Células Hep G2 , Sistemas de Liberación de Medicamentos/métodos , Portadores de Fármacos/química , Dióxido de Silicio/química , Liberación de Fármacos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Nanopartículas/química , Nanopartículas/administración & dosificación , Extractos Vegetales/química , Extractos Vegetales/administración & dosificación , Extractos Vegetales/farmacología , Sistema de Administración de Fármacos con Nanopartículas/química , Antineoplásicos/farmacología , Antineoplásicos/administración & dosificación
10.
Molecules ; 29(8)2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38675668

RESUMEN

In recent years, the frequency of strokes has been on the rise year by year and has become the second leading cause of death around the world, which is characterized by a high mortality rate, high recurrence rate, and high disability rate. Ischemic strokes account for a large percentage of strokes. A reperfusion injury in ischemic strokes is a complex cascade of oxidative stress, neuroinflammation, immune infiltration, and mitochondrial damage. Conventional treatments are ineffective, and the presence of the blood-brain barrier (BBB) leads to inefficient drug delivery utilization, so researchers are turning their attention to nano-drug delivery systems. Functionalized nano-drug delivery systems have been widely studied and applied to the study of cerebral ischemic diseases due to their favorable biocompatibility, high efficiency, strong specificity, and specific targeting ability. In this paper, we briefly describe the pathological process of reperfusion injuries in strokes and focus on the therapeutic research progress of nano-drug delivery systems in ischemic strokes, aiming to provide certain references to understand the progress of research on nano-drug delivery systems (NDDSs).


Asunto(s)
Barrera Hematoencefálica , Accidente Cerebrovascular Isquémico , Humanos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Animales , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/efectos de los fármacos , Sistemas de Liberación de Medicamentos , Daño por Reperfusión/tratamiento farmacológico , Sistema de Administración de Fármacos con Nanopartículas/química , Nanopartículas/química , Isquemia Encefálica/tratamiento farmacológico
11.
Ageing Res Rev ; 97: 102291, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38614367

RESUMEN

The administration of promising medications for the treatment of neurodegenerative disorders (NDDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) is significantly hampered by the blood-brain barrier (BBB). Nanotechnology has recently come to light as a viable strategy for overcoming this obstacle and improving drug delivery to the brain. With a focus on current developments and prospects, this review article examines the use of nanoparticles to overcome the BBB constraints to improve drug therapy for AD The potential for several nanoparticle-based approaches, such as those utilizing lipid-based, polymeric, and inorganic nanoparticles, to enhance drug transport across the BBB are highlighted. To shed insight on their involvement in aiding effective drug transport to the brain, methods of nanoparticle-mediated drug delivery, such as surface modifications, functionalization, and particular targeting ligands, are also investigated. The article also discusses the most recent findings on innovative medication formulations encapsulated within nanoparticles and the therapeutic effects they have shown in both preclinical and clinical testing. This sector has difficulties and restrictions, such as the need for increased safety, scalability, and translation to clinical applications. However, the major emphasis of this review aims to provide insight and contribute to the knowledge of how nanotechnology can potentially revolutionize the worldwide treatment of NDDs, particularly AD, to enhance clinical outcomes.


Asunto(s)
Enfermedad de Alzheimer , Barrera Hematoencefálica , Sistemas de Liberación de Medicamentos , Nanopartículas , Humanos , Enfermedad de Alzheimer/tratamiento farmacológico , Sistemas de Liberación de Medicamentos/métodos , Animales , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Nanopartículas/administración & dosificación , Sistema de Administración de Fármacos con Nanopartículas
12.
Eur J Pharm Biopharm ; 199: 114279, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38588829

RESUMEN

Our study aimed to develop a virucidal throat spray using bioactive compounds and excipients, focusing on the preparation of Curcumin (CUR) in a self-nano emulsifying drug delivery system (SNEDDS). Two molecular docking studies against SARS-CoV-2 targets guided the selection of proper oil, surfactant, co-surfactant, and natural bioactive that would maximize the antiviral activity of the throat spray. Two self-nanoemulsifying formulas that were diluted with different vehicles to prepare eight CUR-loaded SNESNS (self-nanoemulsifying self-nanosuspension) formulas. In vitro characterization studies and in vitro anti-SARS-CoV-2 effect revealed that the optimal formula, consisted of 20 % Anise oil, 70 % Tween 80, 10 % PEG 400, and 0.1 %w/w CUR, diluted with DEAE-Dx. Preclinical toxicity tests on male rats confirmed the safety of a mild throat spray dose (5 µg/mL CUR). In a rat model of acute pharyngitis induced by ammonia, post-treatment with the optimal formula of CUR loaded SNESNS for one week significantly reduced elevated proinflammatory markers (TNF-α, IL6, MCP1, and IL8). In conclusion, our CUR-loaded SNESNS formula, at 5 µg/mL concentration, shows promising effect as a prophylactic throat spray against SARS-CoV-2 and as a treatment for pharyngitis.


Asunto(s)
Antivirales , Tratamiento Farmacológico de COVID-19 , COVID-19 , Excipientes , Faringitis , SARS-CoV-2 , Animales , Faringitis/tratamiento farmacológico , Excipientes/química , Ratas , Masculino , Antivirales/administración & dosificación , Antivirales/farmacología , Antivirales/química , SARS-CoV-2/efectos de los fármacos , COVID-19/prevención & control , Curcumina/administración & dosificación , Curcumina/farmacología , Humanos , Simulación del Acoplamiento Molecular , Ratas Sprague-Dawley , Sistema de Administración de Fármacos con Nanopartículas/química , Chlorocebus aethiops
13.
Cancer Med ; 13(5): e7010, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38491817

RESUMEN

Cancer remains a leading cause of death worldwide, necessitating the development of innovative and more effective treatment strategies. Conventional cancer treatments often suffer from limitations such as systemic toxicity, poor pharmacokinetics, and drug resistance. Recently, there has been growing attention to utilizing natural compounds derived from various sources as possible cancer therapeutics. Natural compounds have demonstrated diverse bioactive properties, including antioxidant, anti-inflammatory, and antitumor effects, making them attractive candidates for cancer treatment. However, their limited solubility and bioavailability present challenges for effective delivery to cancer cells. To overcome these limitations, researchers have turned to nanotechnology-based drug delivery systems. Nanoparticles, with their small size and unique properties, can encapsulate therapeutic agents and offer benefits such as improved solubility, prolonged drug release, enhanced cellular uptake, and targeted delivery. Functionalizing nanoparticles with specific ligands further enhances their precision in recognizing and binding to cancer cells. Combining natural compounds with nanotechnology holds great promise in achieving efficient and safe cancer treatments by enhancing bioavailability, pharmacokinetics, and selectivity toward cancer cells. This review article provides an overview of the advancements in utilizing natural substances and nanotechnology-based drug delivery systems for cancer treatment. It discusses the benefits and drawbacks of various types of nanoparticles, as well as the characteristics of natural compounds that make them appealing for cancer therapy. Additionally, current research on natural substances and nanoparticles in preclinical and clinical settings is highlighted. Finally, the challenges and future perspectives in developing natural compound-nanoparticle-based cancer therapies are discussed.


Asunto(s)
Antineoplásicos , Nanopartículas , Neoplasias , Humanos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Sistema de Administración de Fármacos con Nanopartículas , Sistemas de Liberación de Medicamentos , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Nanopartículas/química
14.
Int J Nanomedicine ; 19: 2823-2849, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38525013

RESUMEN

Currently, pancreatic cancer (PC) is one of the most lethal malignant tumors. PC is typically diagnosed at a late stage, exhibits a poor response to conventional treatment, and has a bleak prognosis. Unfortunately, PC's survival rate has not significantly improved since the 1960s. Cancer-associated fibroblasts (CAFs) are a key component of the pancreatic tumor microenvironment (TME). They play a vital role in maintaining the extracellular matrix and facilitating the intricate communication between cancer cells and infiltrated immune cells. Exploring therapeutic approaches targeting CAFs may reverse the current landscape of PC therapy. In recent years, nano-drug delivery systems have evolved rapidly and have been able to accurately target and precisely release drugs with little or no toxicity to the whole body. In this review, we will comprehensively discuss the origin, heterogeneity, potential targets, and recent advances in the nano-drug delivery system of CAFs in PC. We will also propose a novel integrated treatment regimen that utilizes a nano-drug delivery system to target CAFs in PC, combined with radiotherapy and immunotherapy. Additionally, we will address the challenges that this regimen currently faces.


Asunto(s)
Fibroblastos Asociados al Cáncer , Neoplasias Pancreáticas , Humanos , Sistema de Administración de Fármacos con Nanopartículas , Neoplasias Pancreáticas/tratamiento farmacológico , Inmunoterapia , Páncreas , Microambiente Tumoral
15.
Artículo en Inglés | MEDLINE | ID: mdl-38528388

RESUMEN

The conventional therapeutic treatment of triple-negative breast cancer (TNBC) is negatively influenced by the development of tumor cell drug resistant, and systemic toxicity of therapeutic agents due to off-target activity. In accordance with research findings, nanoparticles (NPs) responsive to the tumor microenvironment (TME) have been discovered for providing opportunities to selectively target tumor cells via active targeting or Enhanced Permeability and Retention (EPR) effect. The combination of the TME control and therapeutic NPs offers promising solutions for improving the prognosis of the TNBC because the TME actively participates in tumor growth, metastasis, and drug resistance. The NP-based systems leverage stimulus-responsive mechanisms, such as low pH value, hypoxic, excessive secretion enzyme, concentration of glutathione (GSH)/reactive oxygen species (ROS), and high concentration of Adenosine triphosphate (ATP) to combat TNBC progression. Concurrently, NP-based stimulus-responsive introduces a novel approach for drug dosage design, administration, and modification of the pharmacokinetics of conventional chemotherapy and immunotherapy drugs. This review provides a comprehensive examination of the strengths, limitations, applications, perspectives, and future expectations of both novel and traditional stimulus-responsive NP-based drug delivery systems for improving outcomes in the medical practice of TNBC. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.


Asunto(s)
Antineoplásicos , Nanopartículas , Neoplasias de la Mama Triple Negativas , Humanos , Antineoplásicos/uso terapéutico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Sistema de Administración de Fármacos con Nanopartículas , Sistemas de Liberación de Medicamentos , Nanomedicina , Microambiente Tumoral , Nanopartículas/uso terapéutico
16.
Phytomedicine ; 128: 155521, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38489891

RESUMEN

BACKGROUND: The ancient Chinese herb Salvia miltiorrhiza Bunge (Danshen), plays the important role in cardiovascular and cerebrovascular disease. Furthermore, Danshen could also be used for curing carcinogenesis. Up to now, the anti-tumor effects of the main active constituents of Danshen have made great progress. However, the bioavailability of the active constituents of Danshen were restricted by their unique physical characteristics, like low oral bioavailability, rapid degradation in vivo and so on. PURPOSE: With the leap development of nano-delivery systems, the shortcomings of the active constituents of Danshen have been greatly ameliorated. This review tried to summarize the recent progress of the active constituents of Danshen based delivery systems used for anti-tumor therapeutics. METHODS: A systematic literature search was conducted using 5 databases (Embase, Google scholar, PubMed, Scopus and Web of Science databases) for the identification of relevant data published before September 2023. The words "Danshen", "Salvia miltiorrhiza", "Tanshinone", "Salvianolic acid", "Rosmarinic acid", "tumor", "delivery", "nanomedicine" and other active ingredients contained in Danshen were searched in the above databases to gather information about pharmaceutical decoration for the active constituents of Danshen used for anti-tumor therapeutics. RESULTS: The main extracts of Danshen could inhibit the proliferation of tumor cells effectively and a great deal of studies were conducted to design drug delivery systems to ameliorate the anti-tumor effect of the active contents of Danshen through different ways, like improving bioavailability, increasing tumor targeting ability, enhancing biological barrier permeability and co-delivering with other active agents. CONCLUSION: This review systematically represented recent progress of pharmaceutical decorations for the active constituents of Danshen used for anti-tumor therapeutics, revealing the diversity of nano-decoration skills and trying to inspire more designs of Danshen based nanodelivery systems, with the hope that bringing the nanomedicine of the active constituents of Danshen for anti-tumor therapeutics from bench to bedside in the near future.


Asunto(s)
Antineoplásicos Fitogénicos , Medicamentos Herbarios Chinos , Salvia miltiorrhiza , Salvia miltiorrhiza/química , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Humanos , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/farmacología , Sistemas de Liberación de Medicamentos , Animales , Neoplasias/tratamiento farmacológico , Sistema de Administración de Fármacos con Nanopartículas/química , Nanopartículas/química
17.
Mol Pharm ; 21(5): 2148-2162, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38536949

RESUMEN

Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer for which effective therapies are lacking. Targeted remodeling of the immunosuppressive tumor microenvironment (TME) and activation of the body's immune system to fight tumors with well-designed nanoparticles have emerged as pivotal breakthroughs in tumor treatment. To simultaneously remodel the immunosuppressive TME and trigger immune responses, we designed two potential therapeutic nanodelivery systems to inhibit TNBC. First, the bromodomain-containing protein 4 (BRD4) inhibitor JQ1 and the cyclooxygenase-2 (COX-2) inhibitor celecoxib (CXB) were coloaded into chondroitin sulfate (CS) to obtain CS@JQ1/CXB nanoparticles (NPs). Then, the biomimetic nanosystem MM@P3 was prepared by coating branched polymer poly(ß-amino ester) self-assembled NPs with melittin embedded macrophage membranes (MM). Both in vitro and in vivo, the CS@JQ1/CXB and MM@P3 NPs showed excellent immune activation efficiencies. Combination treatment exhibited synergistic cytotoxicity, antimigration ability, and apoptosis-inducing and immune activation effects on TNBC cells and effectively suppressed tumor growth and metastasis in TNBC tumor-bearing mice by activating the tumor immune response and inhibiting angiogenesis. In summary, this study offers a novel combinatorial immunotherapeutic strategy for the clinical TNBC treatment.


Asunto(s)
Azepinas , Celecoxib , Triazoles , Neoplasias de la Mama Triple Negativas , Microambiente Tumoral , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/inmunología , Neoplasias de la Mama Triple Negativas/patología , Microambiente Tumoral/efectos de los fármacos , Animales , Femenino , Ratones , Humanos , Celecoxib/administración & dosificación , Línea Celular Tumoral , Sulfatos de Condroitina/química , Sulfatos de Condroitina/administración & dosificación , Nanopartículas/química , Nanopartículas/administración & dosificación , Meliteno/administración & dosificación , Meliteno/química , Apoptosis/efectos de los fármacos , Sistema de Administración de Fármacos con Nanopartículas/química , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones Endogámicos BALB C , Inhibidores de la Ciclooxigenasa 2/administración & dosificación , Inhibidores de la Ciclooxigenasa 2/farmacología , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Polímeros/química , Ratones Desnudos , Sistemas de Liberación de Medicamentos/métodos
18.
Food Res Int ; 180: 114068, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38395544

RESUMEN

Gallic acid (GA), a dietary phenolic acid with potent antioxidant activity, is widely distributed in edible plants. GA has been applied in the food industry as an antimicrobial agent, food fresh-keeping agent, oil stabilizer, active food wrap material, and food processing stabilizer. GA is a potential dietary supplement due to its health benefits on various functional disorders associated with oxidative stress, including renal, neurological, hepatic, pulmonary, reproductive, and cardiovascular diseases. GA is rapidly absorbed and metabolized after oral administration, resulting in low bioavailability, which is susceptible to various factors, such as intestinal microbiota, transporters, and metabolism of galloyl derivatives. GA exhibits a tendency to distribute primarily to the kidney, liver, heart, and brain. A total of 37 metabolites of GA has been identified, and decarboxylation and dihydroxylation in phase I metabolism and sulfation, glucuronidation, and methylation in phase Ⅱ metabolism are considered the main in vivo biotransformation pathways of GA. Different types of nanocarriers, such as polymeric nanoparticles, dendrimers, and nanodots, have been successfully developed to enhance the health-promoting function of GA by increasing bioavailability. GA may induce drug interactions with conventional drugs, such as hydroxyurea, linagliptin, and diltiazem, due to its inhibitory effects on metabolic enzymes, including cytochrome P450 3A4 and 2D6, and transporters, including P-glycoprotein, breast cancer resistance protein, and organic anion-transporting polypeptide 1B3. In conclusion, in-depth studies of GA on food industry applications, health benefits, bioavailability, nano-delivery systems, and drug interactions have laid the foundation for its comprehensive application as a food additive and dietary supplement.


Asunto(s)
Antioxidantes , Ácido Gálico , Antioxidantes/farmacología , Ácido Gálico/metabolismo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/metabolismo , Disponibilidad Biológica , Sistema de Administración de Fármacos con Nanopartículas , Proteínas de Neoplasias/metabolismo , Interacciones Farmacológicas , Proteínas de Transporte de Membrana/metabolismo , Industria de Alimentos
19.
ACS Biomater Sci Eng ; 10(3): 1302-1322, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38346448

RESUMEN

The treatment of bone defects has been a long-standing challenge in clinical practice. Among the various bone tissue engineering approaches, there has been substantial progress in the development of drug delivery systems based on functional drugs and appropriate carrier materials owing to technological advances in recent years. A large number of materials based on functional nanocarriers have been developed and applied to improve the complex osteogenic microenvironment, including for promoting osteogenic activity, inhibiting osteoclast activity, and exerting certain antibacterial effects. This Review discusses the physicochemical properties, drug loading mechanisms, advantages and disadvantages of nanoparticles (NPs) used for constructing drug delivery systems. In addition, we provide an overview of the osteogenic microenvironment regulation mechanism of drug delivery systems based on nanoparticle (NP) carriers and the construction strategies of drug delivery systems. Finally, the advantages and disadvantages of NP carriers are summarized along with their prospects and future research trends in bone tissue engineering. This Review thus provides advanced strategies for the design and application of drug delivery systems based on NPs in the treatment of bone defects.


Asunto(s)
Sistema de Administración de Fármacos con Nanopartículas , Nanopartículas , Sistemas de Liberación de Medicamentos , Regeneración Ósea/fisiología , Nanopartículas/uso terapéutico , Nanopartículas/química , Ingeniería de Tejidos
20.
ACS Appl Bio Mater ; 7(3): 1643-1655, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38366996

RESUMEN

Pathogens and pests pose significant threats to global crop productivity and plant immunity, necessitating urgent measures from researchers to prevent pathogen contamination and pest damage to crops. A natural plant-based antibacterial agent, eugenol (EUG), has demonstrated excellent antimicrobial and insect repellent capabilities, but the characteristics of volatilization and poor dissolution limit the practical application. The nanoization of pesticide formulations holds promise in the development of highly effective pesticides for antibacterial and insecticidal purposes. Herein, a eugenol-loaded nano delivery system (EUG@CMC-PGMA-CS) was synthesized using glycidyl methacrylate (GMA) as a functional monomer to connect carrier core structure carboxymethyl cellulose (CMC) with shell structure chitosan (CS), and EUG was encapsulated within the carrier. EUG@CMC-PGMA-CS demonstrated excellent leaf affinity, with minimum contact angles (CAs) of 37.83 and 70.52° on hydrophilic and hydrophobic vegetable leaf surfaces, respectively. Moreover, the maximum liquid holding capacity (LHC) of EUG@CMC-PGMA-CS on both hydrophilic and hydrophobic vegetable leaf surfaces demonstrates a noteworthy 55.24% enhancement compared to the LHC of pure EUG. The in vitro release curve of EUG@CMC-PGMA-CS exhibited an initial burst followed by stable sustained release. It is with satisfaction that the nano delivery system demonstrated exceptional antibacterial properties against S. aureus and satisfactory insecticidal efficacy against Spodoptera litura. The development of this eugenol-loaded nano delivery system holds significant potential for enhanced antibacterial and insect repellents in agriculture, paving the way for the application of volatile bioactive substances.


Asunto(s)
Eugenol , Repelentes de Insectos , Eugenol/farmacología , Eugenol/química , Carboximetilcelulosa de Sodio/química , Sistema de Administración de Fármacos con Nanopartículas , Staphylococcus aureus , Antibacterianos/farmacología
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