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1.
Drug Deliv ; 31(1): 2372269, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38956885

RESUMO

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.


Assuntos
Acne Vulgar , Portadores de Fármacos , Folículo Piloso , Polímeros , Folículo Piloso/efeitos dos fármacos , Folículo Piloso/metabolismo , Acne Vulgar/tratamento farmacológico , Humanos , Polímeros/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas , Administração Cutânea , Animais , Sistemas de Liberação de Fármacos por Nanopartículas/química
2.
Int J Nanomedicine ; 19: 5125-5138, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38855730

RESUMO

Purpose: Breast cancer is a prevalent malignancy among women worldwide, and malignancy is closely linked to the tumor microenvironment (TME). Here, we prepared mixed nano-sized formulations composed of pH-sensitive liposomes (Ber/Ru486@CLPs) and small-sized nano-micelles (Dox@CLGs). These liposomes and nano-micelles were modified by chondroitin sulfate (CS) to selectively target breast cancer cells. Methods: Ber/Ru486@CLPs and Dox@CLGs were prepared by thin-film dispersion and ethanol injection, respectively. To mimic actual TME, the in vitro "condition medium of fibroblasts + MCF-7" cell model and in vivo "4T1/NIH-3T3" co-implantation mice model were established to evaluate the anti-tumor effect of drugs. Results: The physicochemical properties showed that Dox@CLGs and Ber/Ru486@CLPs were 28 nm and 100 nm in particle size, respectively. In vitro experiments showed that the mixed formulations significantly improved drug uptake and inhibited cell proliferation and migration. The in vivo anti-tumor studies further confirmed the enhanced anti-tumor capabilities of Dox@CLGs + Ber/Ru486@CLPs, including smaller tumor volumes, weak collagen deposition, and low expression levels of α-SMA and CD31 proteins, leading to a superior anti-tumor effect. Conclusion: In brief, this combination therapy based on Dox@CLGs and Ber/Ru486@CLPs could effectively inhibit tumor development, which provides a promising approach for the treatment of breast cancer.


Assuntos
Neoplasias da Mama , Proliferação de Células , Doxorrubicina , Lipossomos , Microambiente Tumoral , Microambiente Tumoral/efeitos dos fármacos , Animais , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Humanos , Camundongos , Lipossomos/química , Células MCF-7 , Doxorrubicina/farmacologia , Doxorrubicina/química , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacocinética , Proliferação de Células/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Células NIH 3T3 , Sulfatos de Condroitina/química , Sulfatos de Condroitina/farmacologia , Tamanho da Partícula , Sistemas de Liberação de Fármacos por Nanopartículas/química , Sistemas de Liberação de Medicamentos/métodos , Movimento Celular/efeitos dos fármacos , Nanopartículas/química
3.
Front Immunol ; 15: 1380229, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38911867

RESUMO

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.


Assuntos
Neoplasias do Colo , Diterpenos , Micelas , Polissacarídeos , Animais , Neoplasias do Colo/tratamento farmacológico , Diterpenos/química , Diterpenos/farmacologia , Diterpenos/administração & dosagem , Humanos , Camundongos , Linhagem Celular Tumoral , Polissacarídeos/química , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Sistemas de Liberação de Medicamentos , Ensaios Antitumorais Modelo de Xenoenxerto , Portadores de Fármacos/química , Nanopartículas/química , Sistemas de Liberação de Fármacos por Nanopartículas/química , Camundongos Nus , Camundongos Endogâmicos BALB C
4.
Int J Nanomedicine ; 19: 5953-5972, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38895147

RESUMO

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.


Assuntos
Emulsões , Extratos Vegetais , Viscum album , Extratos Vegetais/química , Extratos Vegetais/administração & dosagem , Viscum album/química , Emulsões/química , Folhas de Planta/química , Sistemas de Liberação de Medicamentos/métodos , Tamanho da Partícula , Sistemas de Liberação de Fármacos por Nanopartículas/química , Nanopartículas/química
5.
Int J Nanomedicine ; 19: 5581-5603, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38882543

RESUMO

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.


Assuntos
Antineoplásicos , Sistemas de Liberação de Fármacos por Nanopartículas , Compostos de Fenilureia , Quinolinas , Humanos , Quinolinas/química , Quinolinas/farmacocinética , Quinolinas/administração & dosagem , Quinolinas/farmacologia , Compostos de Fenilureia/química , Compostos de Fenilureia/farmacocinética , Compostos de Fenilureia/administração & dosagem , Antineoplásicos/química , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Antineoplásicos/farmacocinética , Sistemas de Liberação de Fármacos por Nanopartículas/química , Animais , Microambiente Tumoral/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Nanopartículas/química
6.
Int J Nanomedicine ; 19: 5317-5333, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38859953

RESUMO

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.


Assuntos
Eritrócitos , Síndrome do Desconforto Respiratório , Sinvastatina , Sinvastatina/administração & dosagem , Sinvastatina/farmacocinética , Sinvastatina/química , Síndrome do Desconforto Respiratório/tratamento farmacológico , Eritrócitos/efeitos dos fármacos , Animais , Pulmão/efeitos dos fármacos , Humanos , Masculino , Sistemas de Liberação de Fármacos por Nanopartículas/química , Sistemas de Liberação de Fármacos por Nanopartículas/farmacocinética , Nanopartículas/química , Nanopartículas/administração & dosagem , Camundongos , Polietilenoimina/química , Sistemas de Liberação de Medicamentos/métodos , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética
7.
Sci Adv ; 10(25): eadn2332, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38896625

RESUMO

Satisfactory healing following acute tendon injury is marred by fibrosis. Despite the high frequency of tendon injuries and poor outcomes, there are no pharmacological therapies in use to enhance the healing process. Moreover, systemic treatments demonstrate poor tendon homing, limiting the beneficial effects of potential tendon therapeutics. To address this unmet need, we leveraged our existing tendon healing spatial transcriptomics dataset and identified an area enriched for expression of Acp5 (TRAP) and subsequently demonstrated robust TRAP activity in the healing tendon. This unexpected finding allowed us to refine and apply our existing TRAP binding peptide (TBP) functionalized nanoparticle (NP) drug delivery system (DDS) to facilitate improved delivery of systemic treatments to the healing tendon. To demonstrate the translational potential of this DDS, we delivered niclosamide (NEN), an S100a4 inhibitor. While systemic delivery of free NEN did not alter healing, TBP-NPNEN enhanced both functional and mechanical recovery, demonstrating the translational potential of this approach to enhance the tendon healing process.


Assuntos
Traumatismos dos Tendões , Tendões , Cicatrização , Animais , Cicatrização/efeitos dos fármacos , Traumatismos dos Tendões/tratamento farmacológico , Tendões/efeitos dos fármacos , Tendões/metabolismo , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Camundongos , Sistemas de Liberação de Fármacos por Nanopartículas/química , Modelos Animais de Doenças , Proteínas de Ligação ao Cálcio/metabolismo , Humanos
8.
Int J Nanomedicine ; 19: 4857-4875, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38828195

RESUMO

Brain diseases are the most devastating problem among the world's increasingly aging population, and the number of patients with neurological diseases is expected to increase in the future. Although methods for delivering drugs to the brain have advanced significantly, none of these approaches provide satisfactory results for the treatment of brain diseases. This remains a challenge due to the unique anatomy and physiology of the brain, including tight regulation and limited access of substances across the blood-brain barrier. Nanoparticles are considered an ideal drug delivery system to hard-to-reach organs such as the brain. The development of new drugs and new nanomaterial-based brain treatments has opened various opportunities for scientists to develop brain-specific delivery systems that could improve treatment outcomes for patients with brain disorders such as Alzheimer's disease, Parkinson's disease, stroke and brain tumors. In this review, we discuss noteworthy literature that examines recent developments in brain-targeted nanomedicines used in the treatment of neurological diseases.


Assuntos
Barreira Hematoencefálica , Encéfalo , Sistemas de Liberação de Medicamentos , Nanomedicina , Humanos , Nanomedicina/métodos , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Encéfalo/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Animais , Nanopartículas/química , Encefalopatias/tratamento farmacológico , Sistemas de Liberação de Fármacos por Nanopartículas/química , Sistemas de Liberação de Fármacos por Nanopartículas/farmacocinética , Doença de Parkinson/tratamento farmacológico , Doença de Alzheimer/tratamento farmacológico
9.
J Biomater Appl ; 39(2): 150-161, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38748570

RESUMO

Background: Glycyrrhetinic acid-mediated brucine self-assembled nanomicelles enhance the anti-hepatitis B properties of brucine by improving its water solubility, short half-life, toxicity, and side effects. Brucine (B) is an indole alkaloid extracted from the seeds of Strychnos nux-vomica (Loganiaceae). Purpose: To assess the efficacy of the Brucine-Glycyrrhetnic acid-Polyethylene glycol-3,3'-dithiodipropionic acid-Glycerin monostearate (B-GPSG) in treating hepatitis B, its potential to protect against acute liver injury caused by d-galactosamine and its anti-hepatoma activities were studied. Research Design: The concentration of B-GPSG used in the in vivo and in vitro experiments was 0.63 mg/mL. The rats injected with d-GalN (450 mg/kg) were used as liver injury models. The rats were separated into normal, model, positive, positive control, B-PSG and B-GPSG groups. Hepatoma cells expressing HBV HepG2.2.15 were used for in vitro experiments. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, plate cloning, Hoechst staining and flow cytometry were conducted to explore the mechanism of B-GPSG against hepatitis B. Results: Compared with the model group, the liver coefficient of B-GPSG group decreased (4.59 ± 0.17 vs 5.88 ± 0.42), the content of MDA in rat liver homogenate decreased (12.54 ± 1.81 vs 23.05 ± 2.98), the activity of SOD increased, the activity of ALT and AST in rat serum decreased. In vitro, the IC50 values of B-GPSG group decreased. B-GPSG group effectively inhibited the proliferation and migration of HepG2.2.15 cells. Conclusions: The hepatoprotective effects of B-GPSG nanomicelles, which are attributed to their GA-mediated liver targeting and synergistic actions with brucine, suggest their therapeutic potential against hepatitis B. This development opens up new possibilities for the application of traditional Chinese medicine and nanomedicine in anti-hepatitis B.


Assuntos
Ácido Glicirretínico , Hepatite B , Estricnina , Animais , Ácido Glicirretínico/análogos & derivados , Ácido Glicirretínico/química , Ácido Glicirretínico/farmacologia , Humanos , Células Hep G2 , Hepatite B/tratamento farmacológico , Estricnina/análogos & derivados , Estricnina/farmacologia , Estricnina/administração & dosagem , Estricnina/química , Ratos , Masculino , Ratos Sprague-Dawley , Antivirais/farmacologia , Antivirais/química , Antivirais/administração & dosagem , Fígado/metabolismo , Fígado/efeitos dos fármacos , Sistemas de Liberação de Fármacos por Nanopartículas/química
10.
Zhongguo Zhong Yao Za Zhi ; 49(8): 2117-2127, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-38812227

RESUMO

Piperlongumine(PL), a natural alkaloid extracted from Piperis Longi Fructus, has attracted much attention in recent years because of its strong anti-tumor activity, little toxicity to normal cells, and excellent sensitizing effect combined with chemotherapy and radiotherapy, which endow PL with unique advantages as an anti-tumor drug. However, similar to other alkaloids, PL has low water solubility and poor bioavailability. To improve the application of PL in the clinical treatment of tumors, researchers have constructed various nano-drug delivery systems to increase the efficiency of PL delivery. This paper reviewed the physicochemical properties, anti-tumor mechanism, combined therapies, and nano-drug delivery systems of PL in recent years. The review aimed to provide a reference for further research on the anti-tumor effect and nano-drug delivery system of PL. Moreover, this review is expected to provide a reference for the development and application of PL in the anti-tumor therapies.


Assuntos
Dioxolanos , Neoplasias , Dioxolanos/química , Humanos , Animais , Neoplasias/tratamento farmacológico , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacologia , Sistemas de Liberação de Medicamentos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/administração & dosagem , Sistemas de Liberação de Fármacos por Nanopartículas/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/farmacologia , Piperidonas
11.
Biomed Pharmacother ; 175: 116660, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38701563

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) has an extremely devastating nature with poor prognosis and increasing incidence, making it a formidable challenge in the global fight against cancer-related mortality. In this innovative preclinical investigation, the VCP/p97 inhibitor CB-5083 (CB), miR-142, a PD-L1 inhibitor, and immunoadjuvant resiquimod (R848; R) were synergistically encapsulated in solid lipid nanoparticles (SLNs). These SLNs demonstrated features of peptides targeting PD-L1, EGFR, and the endoplasmic reticulum, enclosed in a pH-responsive polyglutamic (PGA)-polyethylene glycol (PEG) shell. The homogeneous size and zeta potential of the nanoparticles were stable for 28 days at 4°C. The study substantiated the concurrent modulation of key pathways by the CB, miR, and R-loaded nanoformulation, prominently affecting VCP/Bip/ATF6, PD-L1/TGF-ß/IL-4, -8, -10, and TNF-α/IFN-γ/IL-1, -12/GM-CSF/CCL4 pathways. This adaptable nanoformulation induced durable antitumor immune responses and inhibited Panc-02 tumor growth by enhancing T cell infiltration, dendritic cell maturation, and suppressing Tregs and TAMs in mice bearing Panc-02 tumors. Furthermore, tissue distribution studies, biochemical assays, and histological examinations highlighted enhanced safety with PGA and peptide-modified nanoformulations for CB, miR, and/or R in Panc-02-bearing mice. This versatile nanoformulation allows tailored adjustment of the tumor microenvironment, thereby optimizing the localized delivery of combined therapy. These compelling findings advocate the potential development of a pH-sensitive, three-in-one PGA-PEG nanoformulation that combines a VCP inhibitor, a PD-L1 inhibitor, and an immunoadjuvant for cancer treatment via combinatorial chemo-immunotherapy.


Assuntos
Imunoterapia , Nanopartículas , Neoplasias Pancreáticas , Microambiente Tumoral , Animais , Microambiente Tumoral/efeitos dos fármacos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/patologia , Humanos , Imunoterapia/métodos , Camundongos , Linhagem Celular Tumoral , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/imunologia , Carcinoma Ductal Pancreático/patologia , Antígeno B7-H1/antagonistas & inibidores , Sistemas de Liberação de Fármacos por Nanopartículas/química , Feminino , Polietilenoglicóis/química , Inibidores de Checkpoint Imunológico/farmacologia , Lipossomos
12.
Mikrochim Acta ; 191(6): 326, 2024 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740583

RESUMO

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.


Assuntos
Movimento Celular , Quimioterapia Combinada , Nanopartículas , Neoplasias , Dióxido de Silício , Movimento Celular/efeitos dos fármacos , Dióxido de Silício/química , Quimioterapia Combinada/métodos , Neoplasias/tratamento farmacológico , Sistemas de Liberação de Fármacos por Nanopartículas/química , Sistemas de Liberação de Fármacos por Nanopartículas/uso terapêutico , Nanopartículas/química , Nanopartículas/uso terapêutico , Nanopartículas/ultraestrutura , Células A549 , Microscopia Eletrônica de Transmissão , Humanos
13.
Biomater Sci ; 12(12): 3045-3067, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38712883

RESUMO

Various strategies at the microscale/nanoscale have been developed to improve oral absorption of therapeutics. Among them, gastrointestinal (GI)-transporter/receptor-mediated nanosized drug delivery systems (NDDSs) have drawn attention due to their many benefits, such as improved water solubility, improved chemical/physical stability, improved oral absorption, and improved targetability of their payloads. Their therapeutic potential in disease animal models (e.g., solid tumors, virus-infected lungs, metastasis, diabetes, and so on) has been investigated, and could be expanded to disease targeting after systemic/lymphatic circulation, although the detailed paths and mechanisms of endocytosis, endosomal escape, intracellular trafficking, and exocytosis through the epithelial cell lining in the GI tract are still unclear. Thus, this review summarizes and discusses potential GI transporters/receptors, their absorption and distribution, in vivo studies, and potential sequential targeting (e.g., oral absorption and disease targeting in organs/tissues).


Assuntos
Nanopartículas , Humanos , Animais , Administração Oral , Nanopartículas/química , Nanopartículas/administração & dosagem , Sistemas de Liberação de Medicamentos , Sistemas de Liberação de Fármacos por Nanopartículas/química
14.
Yakugaku Zasshi ; 144(5): 511-519, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38692926

RESUMO

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.


Assuntos
Lipossomos , Microscopia de Força Atômica , Nanopartículas , Microscopia de Força Atômica/métodos , Lipídeos/química , Sistemas de Liberação de Medicamentos , Sistemas de Liberação de Fármacos por Nanopartículas/química , Peptídeos/química
15.
Int J Nanomedicine ; 19: 4533-4568, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38799699

RESUMO

Until now, there has been a lack of effective strategies for cancer treatment. Immunotherapy has high potential in treating several cancers but its efficacy is limited as a monotherapy. Chemoimmunotherapy (CIT) holds promise to be widely used in cancer treatment. Therefore, identifying their involvement and potential synergy in CIT approaches is decisive. Nano-based drug delivery systems (NDDSs) are ideal delivery systems because they can simultaneously target immune cells and cancer cells, promoting drug accumulation, and reducing the toxicity of the drug. In this review, we first introduce five current immunotherapies, including immune checkpoint blocking (ICB), adoptive cell transfer therapy (ACT), cancer vaccines, oncolytic virus therapy (OVT) and cytokine therapy. Subsequently, the immunomodulatory effects of chemotherapy by inducing immunogenic cell death (ICD), promoting tumor killer cell infiltration, down-regulating immunosuppressive cells, and inhibiting immune checkpoints have been described. Finally, the NDDSs-mediated collaborative drug delivery systems have been introduced in detail, and the development of NDDSs-mediated CIT nanoparticles has been prospected.


Assuntos
Imunoterapia , Neoplasias , Humanos , Imunoterapia/métodos , Neoplasias/terapia , Neoplasias/imunologia , Animais , Nanopartículas/química , Vacinas Anticâncer/administração & dosagem , Terapia Viral Oncolítica/métodos , Sistemas de Liberação de Fármacos por Nanopartículas/química , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Terapia Combinada/métodos
16.
Int J Pharm ; 658: 124218, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38734273

RESUMO

Alzheimer's disease (AD) is an age-related neurodegenerative disorder that causes severe dementia and memory loss. Surface functionalized poly(lactic-co-glycolic acid) nanoparticles have been reported for better transport through the blood-brain barrier for AD therapy. This study investigated the improved therapeutic potential of berberine-loaded poly(lactic-co-glycolic acid)/Tet-1 peptide nanoparticles (BBR/PLGA-Tet NPs) in a rat model of sporadic AD. BBR was loaded into the PLGA-Tet conjugate. BBR/PLGA-Tet NPs were physicochemically and morphologically characterized. AD was achieved by bilateral intracerebroventricular (ICV) injection of streptozotocin (STZ). Cognitively impaired rats were divided into STZ, STZ + BBR, STZ + BBR/PLGA-Tet NPs, and STZ + PLGA-Tet NPs groups. Cognitive improvement was assessed using the Morris Water Maze. Brain acetylcholinesterase and monoamine oxidase activities, amyloid ß42 (Aß42), and brain glycemic markers were estimated. Further, hippocampal neuroplasticity (BDNF, pCREB, and pERK/ERK), Tau pathogenesis (pGSK3ß/GSK3ß, Cdk5, and pTau), inflammatory, and apoptotic markers were evaluated. Finally, histopathological changes were monitored. ICV-STZ injection produces AD-like pathologies evidenced by Aß42 deposition, Tau hyperphosphorylation, impaired insulin signaling and neuroplasticity, and neuroinflammation. BBR and BBR/PLGA-Tet NPs attenuated STZ-induced hippocampal damage, enhanced cognitive performance, and reduced Aß42, Tau phosphorylation, and proinflammatory responses. BBR/PLGA-Tet NPs restored neuroplasticity, cholinergic, and monoaminergic function, which are critical for cognition and brain function. BBR/PLGA-Tet NPs may have superior therapeutic potential in alleviating sporadic AD than free BBR due to their bioavailability, absorption, and brain uptake.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Modelos Animais de Doenças , Hipocampo , Nanopartículas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Estreptozocina , Proteínas tau , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/induzido quimicamente , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/administração & dosagem , Masculino , Nanopartículas/química , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Proteínas tau/metabolismo , Ratos , Peptídeos beta-Amiloides/metabolismo , Fragmentos de Peptídeos/administração & dosagem , Ratos Sprague-Dawley , Sistemas de Liberação de Fármacos por Nanopartículas/química , Portadores de Fármacos/química , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Aprendizagem em Labirinto/efeitos dos fármacos , Ratos Wistar
17.
Nat Commun ; 15(1): 4366, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38777821

RESUMO

Rapid uptake of nanoparticles by mononuclear phagocyte system (MPS) significantly hampers their therapeutic efficacy. Temporal MPS blockade is one of the few ways to overcome this barrier - the approach rediscovered many times under different names but never extensively used in clinic. Using meta-analysis of the published data we prove the efficacy of this technique for enhancing particle circulation in blood and their delivery to tumours, describe a century of its evolution and potential combined mechanism behind it. Finally, we discuss future directions of the research focusing on the features essential for successful clinical translation of the method.


Assuntos
Sistemas de Liberação de Medicamentos , Sistema Fagocitário Mononuclear , Nanopartículas , Humanos , Sistema Fagocitário Mononuclear/metabolismo , Nanopartículas/química , Sistemas de Liberação de Medicamentos/métodos , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Animais , Sistemas de Liberação de Fármacos por Nanopartículas/química
18.
Int J Pharm ; 658: 124192, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38703931

RESUMO

Ocular delivery is the most challenging aspect in the field of pharmaceutical research. The major hurdle for the controlled delivery of drugs to the eye includes the physiological static barriers such as the complex layers of the cornea, sclera and retina which restrict the drug from permeating into the anterior and posterior segments of the eye. Recent years have witnessed inventions in the field of conventional and nanocarrier drug delivery which have shown considerable enhancement in delivering small to large molecules across the eye. The dynamic challenges associated with conventional systems include limited drug contact time and inadequate ocular bioavailability resulting from solution drainage, tear turnover, and dilution or lacrimation. To this end, various bioactive-based nanosized carriers including liposomes, ethosomes, niosomes, dendrimer, nanogel, nanofibers, contact lenses, nanoprobes, selenium nanobells, nanosponge, polymeric micelles, silver nanoparticles, and gold nanoparticles among others have been developed to circumvent the limitations associated with the conventional dosage forms. These nanocarriers have been shown to achieve enhanced drug permeation or retention and prolong drug release in the ocular tissue due to their better tissue adherence. The surface charge and the size of nanocarriers (10-1000 nm) are the important key factors to overcome ocular barriers. Various nanocarriers have been shown to deliver active therapeutic molecules including timolol maleate, ampicillin, natamycin, voriconazole, cyclosporine A, dexamethasone, moxifloxacin, and fluconazole among others for the treatment of anterior and posterior eye diseases. Taken together, in a nutshell, this extensive review provides a comprehensive perspective on the numerous facets of ocular drug delivery with a special focus on bioactive nanocarrier-based approaches, including the difficulties and constraints involved in the fabrication of nanocarriers. This also provides the detailed invention, applications, biodistribution and safety-toxicity of nanocarriers-based therapeutcis for the ophthalmic delivery.


Assuntos
Administração Oftálmica , Sistemas de Liberação de Medicamentos , Oftalmopatias , Nanopartículas , Animais , Humanos , Disponibilidade Biológica , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Olho/metabolismo , Olho/efeitos dos fármacos , Oftalmopatias/tratamento farmacológico , Sistemas de Liberação de Fármacos por Nanopartículas/química , Nanopartículas/química
19.
Int J Nanomedicine ; 19: 4377-4409, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38774029

RESUMO

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.


Assuntos
AVC Isquêmico , Nanopartículas , Neovascularização Fisiológica , Humanos , AVC Isquêmico/tratamento farmacológico , Animais , Nanopartículas/química , Neovascularização Fisiológica/efeitos dos fármacos , Barreira Hematoencefálica/efeitos dos fármacos , Lipossomos/química , Sistemas de Liberação de Medicamentos/métodos , Sistemas de Liberação de Fármacos por Nanopartículas/química , Angiogênese
20.
Int J Nanomedicine ; 19: 4021-4040, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38736657

RESUMO

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.


Assuntos
Catarata , Sistemas de Liberação de Medicamentos , Nanomedicina , Humanos , Catarata/tratamento farmacológico , Nanomedicina/métodos , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Animais , Cristalino/efeitos dos fármacos , Extração de Catarata , Sistemas de Liberação de Fármacos por Nanopartículas/química , Soluções Oftálmicas/química , Soluções Oftálmicas/farmacocinética , Soluções Oftálmicas/administração & dosagem
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