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1.
Int J Mol Sci ; 22(12)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200955

RESUMO

Nanocarriers are delivery platforms of drugs, peptides, nucleic acids and other therapeutic molecules that are indicated for severe human diseases. Gliomas are the most frequent type of brain tumor, with glioblastoma being the most common and malignant type. The current state of glioma treatment requires innovative approaches that will lead to efficient and safe therapies. Advanced nanosystems and stimuli-responsive materials are available and well-studied technologies that may contribute to this effort. The present study deals with the development of functional chimeric nanocarriers composed of a phospholipid and a diblock copolymer, for the incorporation, delivery and pH-responsive release of the antiglioma agent TRAM-34 inside glioblastoma cells. Nanocarrier analysis included light scattering, protein incubation and electron microscopy, and fluorescence anisotropy and thermal analysis techniques were also applied. Biological assays were carried out in order to evaluate the nanocarrier nanotoxicity in vitro and in vivo, as well as to evaluate antiglioma activity. The nanosystems were able to successfully manifest functional properties under pH conditions, and their biocompatibility and cellular internalization were also evident. The chimeric nanoplatforms presented herein have shown promise for biomedical applications so far and should be further studied in terms of their ability to deliver TRAM-34 and other therapeutic molecules to glioblastoma cells.


Assuntos
Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Glioma/tratamento farmacológico , Lipossomos/administração & dosagem , Nanopartículas/administração & dosagem , Polímeros/química , Pirazóis/administração & dosagem , Apoptose , Proliferação de Células , Glioma/metabolismo , Glioma/patologia , Humanos , Concentração de Íons de Hidrogênio , Lipossomos/química , Nanopartículas/química , Células Tumorais Cultivadas
2.
Molecules ; 26(13)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202852

RESUMO

Nano-based particles synthesized via green routes have a particular structure that is useful in biomedical applications as they provide cheap, eco-friendly, and non-toxic nanoparticles. In the present study, we reported the effect of various concentrations of Zinc oxide nanoparticles synthesized using A. lebbeck stem bark extract (ZnO NPsAL) as stabilizing agent on rat biochemical profiles and tissue morphology. Adult Wistar rats weighing 170 ± 5 g were randomly classified into eight groups of five rats each; Group A served as a control fed with normal diet and water. Groups B1, B2, C1, C2, D1, D2, and E were treated with 40 mg/kg and 80 mg/kg of the 0.01, 0.05, and 0.1 M biosynthesized ZnO NPsAL and zinc nitrate daily by the gavage method, respectively. The rats were anesthetized 24 h after the last treatment, blood samples, kidney, heart, and liver tissues were collected for biochemical and histopathological analysis. The rats mean body weight, serum alkaline phosphatase, alanine aminotransferase, creatinine, urea, bilirubin, protein, albumin, globulin, total cholesterol, triacylglycerol, and high-density lipoprotein were significantly altered with an increased concentration of biosynthesized ZnO NPsAL when compared with the control group (p < 0.05; n ≥ 5). Furthermore, histopathological analysis of treated rats' kidney, heart, and liver tissue revealed vascular congestion, tubular necrosis, inflammation, and cytoplasmic vacuolation. Biosynthesized ZnO NPsAL showed significant alteration in biochemical parameters and tissue morphology in rats with increasing concentrations of the nanoparticles.


Assuntos
Albizzia/química , Nanopartículas , Casca de Planta/química , Extratos Vegetais/química , Óxido de Zinco , Animais , Masculino , Nanopartículas/administração & dosagem , Nanopartículas/química , Nanopartículas/uso terapêutico , Especificidade de Órgãos , Ratos , Ratos Wistar , Óxido de Zinco/efeitos adversos , Óxido de Zinco/química , Óxido de Zinco/farmacologia
3.
Int J Nanomedicine ; 16: 4527-4544, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34276212

RESUMO

Background: Chemotherapeutic drugs used for tumor treatments often show limited efficiency due to their short lifetime, nonspecific delivery, and slow or insufficient intracellular drug release, and also, they can cause severe system or organ toxicity. The development of chemotherapeutic nanomedicines with high efficacy and satisfactory safety still remains a challenge for current tumor chemotherapy. Methods: A novel type of conjugate was synthesized using hydroxyethyl starch (HES) as a carrier while binding doxorubicin (DOX) onto HES backbone through a pH/redox responsive linker containing both disulfide and hydrazone bonds in series. The built conjugates were self-assembled into nanoparticles (NPs) (HES-SS-hyd-DOX NPs) for achieving enhanced antitumor therapy and adequate safety. Results: HES-SS-hyd-DOX NPs had a certain ability for the tumor-orientated drug accumulation and were capable of releasing DOX itself rather than DOX derivatives. It was found that the pH/redox responsive linkage enabled the NPs to achieve fast and sufficient intracellular drug release. Based on the tumor-bearing mouse model, antitumor results demonstrated that these NPs were able to inhibit the growth of the advanced tumors with significantly enhanced efficacy when compared to free DOX, and to those conjugate NPs containing only a single responsive or unresponsive bond. Besides, HES-SS-hyd-DOX NPs also showed adequate safety to the normal organs of the treated mice. Conclusion: The pH/redox responsive linkage in HES-SS-hyd-DOX was found to play a critical role in mediating the drug accumulation and the fast and sufficient intracellular drug release. The HES-exposed surface of HES-SS-hyd-DOX NPs endowed the NPs with long circulation capability and remarkably reduced the DOX-induced side effects.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Derivados de Hidroxietil Amido/química , Nanopartículas/administração & dosagem , Neoplasias/tratamento farmacológico , Animais , Antibióticos Antineoplásicos/química , Apoptose , Proliferação de Células , Dissulfetos/química , Doxorrubicina/química , Liberação Controlada de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Neoplasias/patologia , Oxirredução , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Int J Nanomedicine ; 16: 4643-4659, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34267516

RESUMO

Purpose: Hypoxia is considered to be obstructive to tumor treatment, but the reduced oxygen surroundings provide a suitable habitat for Bifidobacterium bifidum (BF) to colonize. The anaerobe BF selectively colonizes into tumors following systemic injection due to its preference for the hypoxia in the tumor cores. Therefore, BF may be a potential targeting agent which could be used effectively in tumor treatment. We aimed to determine whether a novel BF-mediated strategy, that was designed to deliver AP-PFH/PLGA NPs (aptamers CCFM641-5-functionalized Perfluorohexane (PFH) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles) by aptamer-directed approach into solid tumor based on the tumor-targeting ability of BF, could improve efficiency of high intensity focused ultrasound (HIFU) treatment of breast cancer. Methods: We synthesized AP-PFH/PLGA NPs using double emulsion method and carbodiimide method. Then, we evaluated targeting ability of AP-PFH/PLGA NPs to BF in vivo. Finally, we studied the efficacy of HIFU ablation based on BF plus AP-PFH/PLGA NPs (BF-mediated HIFU ablation) in tumor. Results: The elaborately designed AP-PFH/PLGA NPs can target BF colonized in tumor to achieve high tumor accumulation, which can significantly enhance HIFU therapeutic efficiency. We also found that, compared with traditional chemotherapy, this therapy not only inhibits tumor growth, but also significantly prolongs the survival time of mice. More importantly, this treatment strategy has no obvious side effects. Conclusion: We successfully established a novel therapy method, BF-mediated HIFU ablation, which provides an excellent platform for highly efficient and non-invasive therapy of tumor.


Assuntos
Bifidobacterium bifidum/metabolismo , Portadores de Fármacos/metabolismo , Nanopartículas/administração & dosagem , Animais , Linhagem Celular Tumoral , Fluorcarbonetos/química , Humanos , Camundongos , Nanopartículas/uso terapêutico , Poliésteres/química
5.
AAPS PharmSciTech ; 22(5): 179, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34128132

RESUMO

With the limitation of solubility and dissolution rate of insoluble drugs, following oral administration, they would rifely prove poor and volatile bioavailability, which may fail to realize its therapeutic value. The drug nanocrystals are perceived as effective tactic for oral administration of insoluble drugs attributes to possess many prominent properties such as elevating dissolution rate and saturation solubility, high drug loading capacity, and improving oral bioavailability. Based on these advantages, the application of nanocrystals in oral drug delivery has acquired significant achievement, and so far more than 20 products of drug nanocrystals have been confirmed in the market. However, the oral absorption of drug nanocrystals is still facing huge challenges due to the limitation of many factors. Intrinsic properties of the drugs and complex physiological environment of the intestinal tract are the two most important factors affecting the oral bioavailability of drugs. In addition, the research on the multi-aspect mechanisms of nanocrystals promoting gastrointestinal absorption and bioavailability has been gradually deepened. In this review, we summarized recent advances of the nanocrystals delivered orally, and provided an overview to the research progress for crossing the intestinal tract transport mechanisms of the nanocrystals by some new research techniques. Meanwhile, the factors relevant to the transport of drug nanocrystals were also elaborated in detail. Graphical Abstract.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Absorção Intestinal/efeitos dos fármacos , Nanopartículas/administração & dosagem , Preparações Farmacêuticas/administração & dosagem , Administração Oral , Animais , Disponibilidade Biológica , Humanos , Absorção Intestinal/fisiologia , Nanopartículas/química , Nanopartículas/metabolismo , Preparações Farmacêuticas/química , Preparações Farmacêuticas/metabolismo , Solubilidade
6.
Int J Nanomedicine ; 16: 3875-3887, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34135582

RESUMO

Background: The hypoxic microenvironment promotes tumor resistance to most treatments, especially highly oxygen-dependent sonodynamic therapy (SDT). Method and Results: In view of the aggravation of hypoxia by oxygen consumption during SDT, a biomimetic drug delivery system was tailored to integrate SDT with hypoxia-specific chemotherapy. In this system, mesoporous titanium dioxide nanoparticles (mTNPs) were developed to deliver the hypoxia-activated prodrug AQ4N with high loading efficiency. Subsequently, a red blood cell (RBC) membrane was coated onto the surface of mTNP@AQ4N. RBC-mTNPs@AQ4N inherited the immune escape ability from RBC membranes, thus efficiently reducing the immunological clearance and improving the work concentration. Upon activation by ultrasound (US), mTNPs as sonosensitizers generate reactive oxide species (ROS), which not only induce apoptosis and necrosis but also disrupt RBC membranes to achieve the US-mediated on-demand release of AQ4N. The released AQ4N was activated by hypoxia to convert into toxic products, which effectively supplemented the inefficiency of SDT in hypoxic tissues. Importantly, SDT-aggravated hypoxia further potentiated this hypoxia-specific chemotherapy of AQ4N. Conclusion: Based on the sequential strategy, RBC-mTNPs@AQ4N exhibited an excellent synergistic therapeutic effect, thus potentially advancing the development of SDT in cancer treatments.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Mama/terapia , Nanopartículas/administração & dosagem , Titânio/química , Terapia por Ultrassom/métodos , Animais , Antraquinonas/administração & dosagem , Antraquinonas/farmacocinética , Antineoplásicos/farmacocinética , Apoptose/efeitos dos fármacos , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Sistemas de Liberação de Medicamentos/métodos , Membrana Eritrocítica , Feminino , Humanos , Células MCF-7 , Camundongos Endogâmicos BALB C , Nanopartículas/uso terapêutico , Porosidade , Espécies Reativas de Oxigênio/metabolismo , Hipóxia Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Int J Nanomedicine ; 16: 3907-3936, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34135584

RESUMO

Any variation in normal cellular function results in mitochondrial dysregulation that occurs in several diseases, including cancer. Such processes as oxidative stress, metabolism, signaling, and biogenesis play significant roles in cancer initiation and progression. Due to their central role in cellular metabolism, mitochondria are favorable therapeutic targets for the prevention and treatment of conditions like neurodegenerative diseases, diabetes, and cancer. Subcellular mitochondria-specific theranostic nanoformulations for simultaneous targeting, drug delivery, and imaging of these organelles are of immense interest in cancer therapy. It is a challenging task to cross multiple barriers to target mitochondria in diseased cells. To overcome these multiple barriers, several mitochondriotropic nanoformulations have been engineered for the transportation of mitochondria-specific drugs. These nanoformulations include liposomes, dendrimers, carbon nanotubes, polymeric nanoparticles (NPs), and inorganic NPs. These nanoformulations are made mitochondriotropic by conjugating them with moieties like dequalinium, Mito-Porter, triphenylphosphonium, and Mitochondria-penetrating peptides. Most of these nanoformulations are meticulously tailored to control their size, charge, shape, mitochondriotropic drug loading, and specific cell-membrane interactions. Recently, some novel mitochondria-selective antitumor compounds known as mitocans have shown high toxicity against cancer cells. These selective compounds form vicious oxidative stress and reactive oxygen species cycles within cancer cells and ultimately push them to cell death. Nanoformulations approved by the FDA and EMA for clinical applications in cancer patients include Doxil, NK105, and Abraxane. The novel use of these NPs still faces tremendous challenges and an immense amount of research is needed to understand the proper mechanisms of cancer progression and control by these NPs. Here in this review, we summarize current advancements and novel strategies of delivering different anticancer therapeutic agents to mitochondria with the help of various nanoformulations.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Mitocôndrias/efeitos dos fármacos , Nanoestruturas/administração & dosagem , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos , Humanos , Lipossomos/administração & dosagem , Lipossomos/química , Lipossomos/farmacologia , Mitocôndrias/metabolismo , Nanopartículas/administração & dosagem , Nanopartículas/química , Nanoestruturas/uso terapêutico , Nanotubos de Carbono , Neoplasias/metabolismo , Neoplasias/patologia , Fosforilação Oxidativa/efeitos dos fármacos , Peptídeos/química , Peptídeos/farmacocinética , Nanomedicina Teranóstica/métodos
8.
Int J Nanomedicine ; 16: 4031-4044, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34140770

RESUMO

Introduction: Topical agents typically remain in the wound site for time duration that are too short to effectively eradicate MRSA tradition formation of BZK that can be maintained within the wound site for longer time periods, should be more effective. Methods: The novel chitosan and poly (D,L-lactide-co-glycoside) nanoparticles loaded with benzalkonium bromide (BZK) were designed, for the promotion wound healing after MRSA infection. The physical characterization of these nanoparticles, as well as their antibacterial activity in vitro, release profile in simulated wound fluid, cell toxicity, anti-biofilm activity, and their ability to improve the skin wound healing in a mouse model were also studied. Results: These novel nanoparticles were found to have a significant antibacterial activity (p<0.01), both in vitro and in vivo test. The stronger anti-biofilm ability of the nanoparticles to inhibit the formation of bacterial biofilms, at a concentration of 3.33 µg/mL, and clear existing bacterial biofilms, at a concentration of 5 mg/mL, compared with its water solution. In addition, significant damage to bacterial cell walls also was found, providing insight into the mechanism of antibacterial activity. Conclusion: Taken together, these results demonstrated the ability of BZK-loaded nanoparticles in the promotion of skin wound healing with MRSA infection. The current findings open a new avenue for nanomedicine development and future clinical applications in the treatment of wounds.


Assuntos
Antibacterianos/farmacologia , Compostos de Benzalcônio/administração & dosagem , Nanopartículas/administração & dosagem , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Compostos de Benzalcônio/farmacocinética , Compostos de Benzalcônio/farmacologia , Biofilmes/efeitos dos fármacos , Quitosana/química , Sistemas de Liberação de Medicamentos , Feminino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Camundongos Endogâmicos BALB C , Nanopartículas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Álcool de Polivinil/administração & dosagem , Álcool de Polivinil/farmacologia , Infecções Cutâneas Estafilocócicas/microbiologia
9.
Int J Nanomedicine ; 16: 3937-3999, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34140768

RESUMO

Surfactants, whose existence has been recognized as early as 2800 BC, have had a long history with the development of human civilization. With the rapid development of nanotechnology in the latter half of the 20th century, breakthroughs in nanomedicine and food nanotechnology using nanoparticles have been remarkable, and new applications have been developed. The technology of surfactant-coated nanoparticles, which provides new functions to nanoparticles for use in the fields of nanomedicine and food nanotechnology, is attracting a lot of attention in the fields of basic research and industry. This review systematically describes these "surfactant-coated nanoparticles" through various sections in order: 1) surfactants, 2) surfactant-coated nanoparticles, application of surfactant-coated nanoparticles to 3) nanomedicine, and 4) food nanotechnology. Furthermore, current progress and problems of the technology using surfactant-coated nanoparticles through recent research reports have been discussed.


Assuntos
Nanomedicina/métodos , Nanopartículas/química , Nanopartículas/uso terapêutico , Tensoativos/química , Animais , Encéfalo/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Alimentos , Humanos , Nanopartículas/administração & dosagem , Nanotecnologia/métodos , Tensoativos/farmacologia
10.
Life Sci ; 279: 119674, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34081992

RESUMO

One of the global alarming prevalent metabolic diseases is Type 2 diabetes mellitus (T2DM) than other diabetes and sustains a substantial burden on public and healthcare systems. This study attempts to endeavor the beneficial effect of chitosan stabilized nanoparticles Ch-SeNPs on combating diabetic nephropathy (DN) after induction of T2DM in rats (DN.STZ-induced T2D). High-fat diet (HFD) and STZ were used for the induction of T2DM in rats, and then they were treated with either metformin alone (MEF) (500 mg/kg b.wt.) or combined with (Ch-SeNPs) (2 mg Se/kg b.wt.) for eight weeks. The microvascular complications in renal tissue of diabetic rats were pronounced by the prevalence of microalbuminuria and elevated levels of urea, creatinine, and BUN. Pronounced oxidative stress with enhanced inflammatory response. In the urine of diabetic rats, a marked increase in Kim 1, ß2-microglobulin, and urinary albumin. Renal morphological alterations were observed in all groups upon induction of T2DM, except for the Ch-SeNPs/MEF group showed noticeable improvements. The expression levels of Aldo-keto reductase AKr1B1, profibrotic protein transforming growth factor-ß1 (TGF-ß1), nestin, desmin, and vimentin, were up-regulated in the diabetic group. Significant down-regulation of their expression and restored antioxidant capacity was observed in the combined-treated group than single treated ones. Ch-SeNPs helped limit the prevalence of TNF-α, IL-6, and IL-1ß while used after T2DM induction by STZ and HFD. Ch-SeNPs/MEF co-therapy could effectively guard the kidneys and reduce the renal tissue injury via inhibiting oxidative stress and restoring glucose hemostasis, which indicates a promising line for treating T2DM nephropathy.


Assuntos
Aldeído Redutase/metabolismo , Quitosana/química , Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/tratamento farmacológico , Rim/efeitos dos fármacos , Nanopartículas/administração & dosagem , Selênio/química , Aldeído Redutase/genética , Animais , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Regulação da Expressão Gênica , Rim/lesões , Rim/metabolismo , Rim/patologia , Testes de Função Renal , Masculino , Nanopartículas/química , Ratos , Ratos Sprague-Dawley
11.
Life Sci ; 279: 119667, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34087280

RESUMO

Estimates indicate that cancer will become the leading cause of mortality worldwide in the future. Tumorigenesis is a complex process that involves self-sufficiency in signs of growth, insensitivity to anti-growth signals, prevention of apoptosis, unlimited replication, sustained angiogenesis, tissue invasion, and metastasis. Cancer stem cells (CSCs) have an important role in tumor development and resistance. Here we will approach phenotypic plasticity capacity, highly efficient DNA repair systems, anti-apoptotic machinery, sustained stemness features, interaction with the tumor microenvironment, and Notch, Wnt, and Hedgehog signaling pathways. The researches about CSCs as a target in cancer treatment has been growing. Many different options have pointed beneficial results, such as pathways and CSC-surface markers targeting. Besides its limitations, nanotherapeutics have emerged as a potential strategy in this context since they aim to improve pharmacokinetics, biodistribution, and reduce the side effects observed in traditional treatments. Nanoparticles have been studied in this field, mostly for drug delivery and a multitherapy approach. Another widely researched approaches in this area are related to heat therapy, such as photothermal therapy, photodynamic therapy and magnetic hyperthermia, besides molecular targeting. This review will contemplate the most relevant studies that have shown the effects of nanotherapeutics. In conclusion, although the studies analyzed are mostly preclinical, we believe that there is strong evidence that nanoparticles can increase the chances of a better prognosis to cancer in the future. It is also essential to transpose these findings to the clinic to confirm and better understand the role of nanotherapeutics in this context.


Assuntos
Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Nanopartículas/administração & dosagem , Neoplasias/tratamento farmacológico , Células-Tronco Neoplásicas/efeitos dos fármacos , Animais , Antineoplásicos/química , Humanos , Nanopartículas/química , Neoplasias/patologia , Células-Tronco Neoplásicas/patologia
12.
AAPS PharmSciTech ; 22(5): 191, 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34169366

RESUMO

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has demonstrated notable clinical activity in cancer immunotherapy, but it is limited by systemic toxicities, poor bioavailability, rapid clearance, and instability in vivo. Nanoparticles (NPs) may overcome these limitations and provide a mechanism for passive targeting of tumors. This study aimed to develop GM-CSF-loaded PLGA/PLGA-PEG NPs and evaluate them in vitro as a potential candidate for in vivo administration. NPs were created by a phase-separation technique that did not require toxic/protein-denaturing solvents or harsh agitation techniques and encapsulated GM-CSF in a more stable precipitated form. NP sizes were within 200 nm for enhanced permeability and retention (EPR) effect with negative zeta potentials, spherical morphology, and high entrapment efficiencies. The optimal formulation was identified by sustained release of approximately 70% of loaded GM-CSF over 24 h, alongside an average size of 143 ± 35 nm and entrapment efficiency of 84 ± 5%. These NPs were successfully freeze-dried in 5% (w/v) hydroxypropyl-ß-cyclodextrin for long-term storage and further characterized. Bioactivity of released GM-CSF was determined by observing GM-CSF receptor activation on murine monocytes and remained fully intact. NPs were not cytotoxic to murine bone marrow-derived macrophages (BMDMs) at concentrations up to 1 mg/mL as determined by MTT and trypan blue exclusion assays. Lastly, NP components generated no significant transcription of inflammation-regulating genes from BMDMs compared to IFNγ+LPS "M1" controls. This report lays the preliminary groundwork to validate in vivo studies with GM-CSF-loaded PLGA/PEG-PLGA NPs for tumor immunomodulation. Overall, these data suggest that in vivo delivery will be well tolerated.


Assuntos
Fator Estimulador de Colônias de Granulócitos e Macrófagos/síntese química , Macrófagos/efeitos dos fármacos , Nanopartículas/química , Poliésteres/síntese química , Polietilenoglicóis/síntese química , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/síntese química , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Composição de Medicamentos , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacocinética , Humanos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas/administração & dosagem , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Poliésteres/administração & dosagem , Poliésteres/farmacocinética , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/farmacocinética
13.
Int J Mol Sci ; 22(10)2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34067699

RESUMO

Gene therapy has the potential to become a staple of 21st-century medicine. However, to overcome the limitations of existing gene-delivery therapies, that is, poor stability and inefficient and delivery and accumulation of nucleic acids (NAs), safe drug-delivery systems (DDSs) allowing the prolonged circulation and expression of the administered genes in vivo are needed. In this review article, the development of DDSs over the past 70 years is briefly described. Since synthetic DDSs can be recognized and eliminated as foreign substances by the immune system, new approaches must be found. Using the body's own cells as DDSs is a unique and exciting strategy and can be used in a completely new way to overcome the critical limitations of existing drug-delivery approaches. Among the different circulatory cells, red blood cells (RBCs) are the most abundant and thus can be isolated in sufficiently large quantities to decrease the complexity and cost of the treatment compared to other cell-based carriers. Therefore, in the second part, this article describes 70 years of research on the development of RBCs as DDSs, covering the most important RBC properties and loading methods. In the third part, it focuses on RBCs as the NA delivery system with advantages and drawbacks discussed to decide whether they are suitable for NA delivery in vivo.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Sistemas de Liberação de Medicamentos/tendências , Eritrócitos/metabolismo , Portadores de Fármacos/metabolismo , Eritrócitos/fisiologia , Humanos , Nanopartículas/administração & dosagem , Ácidos Nucleicos/química , Ácidos Nucleicos/metabolismo , Preparações Farmacêuticas/metabolismo
14.
Fish Shellfish Immunol ; 115: 189-197, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34147613

RESUMO

The present study examines the effectiveness of DNA vaccine against Aeromonas hydrophila through oral route using chitosan-tripolyphosphate (Cs-TPP) nanoparticles encapsulation. The virulent gene of outer membrane protein (OMP) and hemolysin (hly) related to pathogenicity of A. hydrophila was used to construct a DNA vaccine using pVAX1, and the construct was named as pVAX-OMP and pVAX-hly DNA vaccines. The pVAX-OMP and pVAX-hly DNA vaccines were encapsulated by Cs-TPP nanoparticles and size measured by field emission scanning electron microscopy (FE-SEM). The encapsulation efficiency of Cs-TPP nanoparticles was found to be 79.6% for pVAX-OMP DNA and 82.3% for pVAX-hly DNA binding with Cs-TPP nanoparticles. The stability and invitro release profile of plasmid DNA was also determined after encapsulation using DNase and chitosanase. DNA vaccines distribution in tissues was investigated in fish fed with the pVAX-OMP, pVAX-hly and pVAX-OMP+pVAX-hly encapsulated in Cs-TPP nanoparticles and confirmed by PCR and multiplex PCR. The results suggest that Cs-TPP nanoparticles encapsulated DNA vaccine delivered into fish by feeding. After oral vaccination of Labeo rohita were challenged with A. hydrophila by intraperitoneal injection. Relatively, gene expression of c- and g-type lysozyme followed by pro- and anti-inflammatory cytokines (Interlukin-10 and Tumor Growth Factor ß) was up-regulated in heart and kidney for pVAX-OMP+pVAX-hly vaccinated group. Moreover, fish fed with pVAX-OMP+pVAX-hly encapsulated in Cs-TPP nanoparticles had a significantly higher survival rate (76.2%) against A. hydrophila. This study concludes that pVAX-OMP and pVAX-hly DNA vaccines can be delivered orally using Cs-TPP nanoparticles for protection against A. hydrophilainfection.


Assuntos
Vacinas Bacterianas/administração & dosagem , Quitosana/análogos & derivados , Cyprinidae , Doenças dos Peixes/prevenção & controle , Infecções por Bactérias Gram-Negativas/veterinária , Vacinação/veterinária , Vacinas de DNA/administração & dosagem , Administração Oral , Aeromonas hydrophila/fisiologia , Animais , Proteínas da Membrana Bacteriana Externa/imunologia , Quitosana/administração & dosagem , Quitosana/imunologia , Doenças dos Peixes/microbiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/prevenção & controle , Proteínas Hemolisinas/imunologia , Nanopartículas/administração & dosagem
15.
Molecules ; 26(11)2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34064297

RESUMO

Transdermal drug delivery system (TDDS) is an attractive method for drug delivery with convenient application, less first-pass effect, and fewer systemic side effects. Among all generations of TDDS, transdermal nanocarriers show the greatest clinical potential because of their non-invasive properties and high drug delivery efficiency. However, it is still difficult to design optimal transdermal nanocarriers to overcome the skin barrier, control drug release, and achieve targeting. Hence, surface modification becomes a promising strategy to optimize and functionalize the transdermal nanocarriers with enhanced penetration efficiency, controlled drug release profile, and targeting drug delivery. Therefore, this review summarizes the developed transdermal nanocarriers with their transdermal mechanism, and focuses on the surface modification strategies via their different functions.


Assuntos
Portadores de Fármacos , Nanopartículas/administração & dosagem , Administração Cutânea , Animais , Propriedades de Superfície
16.
Nat Commun ; 12(1): 3460, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34103491

RESUMO

Lack or dysfunction of the lymphatics leads to secondary lymphedema formation that seriously reduces the function of the affected organs and results in degradation of quality of life. Currently, there is no definitive treatment option for lymphedema. Here, we utilized nucleoside-modified mRNA encapsulated in lipid nanoparticles (LNPs) encoding murine Vascular Endothelial Growth Factor C (VEGFC) to stimulate lymphatic growth and function and reduce experimental lymphedema in mouse models. We demonstrated that administration of a single low-dose of VEGFC mRNA-LNPs induced durable, organ-specific lymphatic growth and formation of a functional lymphatic network. Importantly, VEGFC mRNA-LNP treatment reversed experimental lymphedema by restoring lymphatic function without inducing any obvious adverse events. Collectively, we present a novel application of the nucleoside-modified mRNA-LNP platform, describe a model for identifying the organ-specific physiological and pathophysiological roles of the lymphatics, and propose an efficient and safe treatment option that may serve as a novel therapeutic tool to reduce lymphedema.


Assuntos
Linfangiogênese/genética , Vasos Linfáticos/patologia , Linfedema/patologia , Nucleosídeos/metabolismo , Fator C de Crescimento do Endotélio Vascular/genética , Animais , Vasos Sanguíneos/patologia , Proliferação de Células/efeitos dos fármacos , Toxina Diftérica/farmacologia , Modelos Animais de Doenças , Células HEK293 , Humanos , Imunidade/efeitos dos fármacos , Injeções Intradérmicas , Lipídeos/administração & dosagem , Lipídeos/química , Vasos Linfáticos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Nanopartículas/administração & dosagem , Nanopartículas/química , Especificidade de Órgãos , Poli C/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Tamoxifeno/farmacologia , Fator C de Crescimento do Endotélio Vascular/administração & dosagem , Fator C de Crescimento do Endotélio Vascular/metabolismo
17.
J Wound Care ; 30(Sup6): S44-S50, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34120463

RESUMO

OBJECTIVE: Little is known about the efficacy of products aiming to prevent radiodermatitis, which affects between 90-95% of women with breast cancer. The use of antioxidants is promising, however, there is a lack of evidenceon their effectiveness. Here, the authors present a clinical trial protocol to evaluate the effects of applying a cream containing nanoparticles with vitamin E to prevent radiodermatitis in patients with breast cancer. METHOD: The protocol recommends that 108 women with breast cancer, receiving radiotherapy, are included in this triple-blinded, randomized, controlled study at an oncology hospital. Patients will be divided in three groups of 36 individuals each: group A will receive a cream with lipid nanoparticles and vitamin E, group B will receive a cream without nanoparticles nor vitamin E, and group C will receive a cream with nanoparticles without vitamin E. The primary endpoints will evaluate the incidence, degree, and time of onset of radiodermatitis. The secondary endpoints will focus on the quality of life, symptoms, and local temperature. Patients will be assessed three times a week, from the start of their radiotherapy treatment to two weeks after the last session. This protocol was approved by the research ethics committee of the institutions involved and registered on an international trials database.


Assuntos
Neoplasias da Mama/radioterapia , Nanopartículas/administração & dosagem , Protetores contra Radiação/administração & dosagem , Radiodermatite/prevenção & controle , Vitamina E/administração & dosagem , Administração Cutânea , Administração Tópica , Protocolos Clínicos , Feminino , Humanos , Nanopartículas/uso terapêutico , Pomadas , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Vitamina E/uso terapêutico
18.
Int J Mol Sci ; 22(11)2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34071329

RESUMO

Avascular transplantation of frozen-thawed testicular tissue fragments represents a potential future technique for fertility restoration in boys with cancer. A significant loss of spermatogonia was observed in xeno-transplants of human tissue most likely due to the hypoxic period before revascularization. To reduce the effect of hypoxia-reoxygenation injuries, several options have already been explored, like encapsulation in alginate hydrogel and supplementation with nanoparticles delivering a necrosis inhibitor (NECINH) or VEGF. While these approaches improved short-term (5 days) vascular surfaces in grafts, neovessels were not maintained up to 21 days; i.e., the time needed for achieving vessel stabilization. To better support tissue grafts, nanoparticles loaded with VEGF, PDGF and NECINH were developed. Testicular tissue fragments from 4-5-week-old mice were encapsulated in calcium-alginate hydrogels, either non-supplemented (control) or supplemented with drug-loaded nanoparticles (VEGF-nanoparticles; VEGF-nanoparticles + PDGF-nanoparticles; NECINH-nanoparticles; VEGF-nanoparticles + NECINH-nanoparticles; and VEGF-nanoparticles + PDGF-nanoparticles + NECINH-nanoparticles) before auto-transplantation. Grafts were recovered after 5 or 21 days for analyses of tissue integrity (hematoxylin-eosin staining), spermatogonial survival (immuno-histo-chemistry for promyelocytic leukemia zinc finger) and vascularization (immuno-histo-chemistry for α-smooth muscle actin and CD-31). Our results showed that a combination of VEGF and PDGF nanoparticles increased vascular maturity and induced a faster maturation of vascular structures in grafts.


Assuntos
Hidrogéis/química , Nanopartículas/administração & dosagem , Neovascularização Fisiológica/efeitos dos fármacos , Fator de Crescimento Derivado de Plaquetas/administração & dosagem , Testículo/transplante , Fator A de Crescimento do Endotélio Vascular/administração & dosagem , Alginatos/química , Animais , Liberação Controlada de Fármacos , Preservação da Fertilidade/métodos , Humanos , Masculino , Camundongos Endogâmicos , Nanopartículas/química , Fator de Crescimento Derivado de Plaquetas/química , Fator de Crescimento Derivado de Plaquetas/farmacocinética , Espermatogônias/efeitos dos fármacos , Testículo/irrigação sanguínea , Fator A de Crescimento do Endotélio Vascular/química , Fator A de Crescimento do Endotélio Vascular/farmacocinética
19.
Int J Mol Sci ; 22(10)2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-34066280

RESUMO

We previously designed a Carbopol gel formulation (N-IND/MEN) based on a combination of indomethacin solid nanoparticles (IND-NPs) and l-menthol, and we reported that the N-IND/MEN showed high transdermal penetration. However, the detailed mechanism for transdermal penetration of IND-NPs was not clearly defined. In this study, we investigated whether endocytosis in the skin tissue of rat and Göttingen minipig is related to the transdermal penetration of IND-NPs using pharmacological inhibitors of endocytosis. The pharmacological inhibitors used in this study are as follows: 54 µM nystatin, a caveolae-mediated endocytosis (CavME) inhibitor; 40 µM dynasore, a clathrin-mediated endocytosis (CME) inhibitor; and 2 µM rottlerin, a micropinocytosis (MP) inhibitor. The N-IND/MEN was prepared by a bead mill method, and the particle size of solid indomethacin was 79-216 nm. In both rat and Göttingen minipig skin, skin penetration of approximately 80% IND-NPs was limited by the stratum corneum (SC), although the penetration of SC was improved by the combination of l-menthol. On the other hand, the treatment of nystatin and dynasore decreased the transdermal penetration of indomethacin in rats and Göttingen minipigs treated with N-IND/MEN. Moreover, in addition to nystatin and dynasore, rottlerin attenuated the transdermal penetration of IND-NPs in the Göttingen minipigs' skin. In conclusion, we found that l-menthol enhanced the SC penetration of IND-NPs. In addition, this study suggests that the SC-passed IND-NPs are absorbed into the skin tissue by energy-dependent endocytosis (CavME, CME, and/or MP pathways) on the epidermis under the SC, resulting in an enhancement in transdermal penetration of IND-NPs. These findings provide significant information for the design of nanomedicines in transdermal formulations.


Assuntos
Endocitose , Indometacina/administração & dosagem , Mentol/administração & dosagem , Nanopartículas/administração & dosagem , Absorção Cutânea , Pele/efeitos dos fármacos , Administração Cutânea , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Antipruriginosos/administração & dosagem , Composição de Medicamentos , Metabolismo Energético , Masculino , Nanopartículas/química , Ratos , Suínos , Porco Miniatura
20.
Cell Mol Life Sci ; 78(12): 5139-5161, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33963442

RESUMO

Immunotherapies have been established as safe and efficient modalities for numerous tumor treatments. The lymphatic system, which is an important system, can modulate the immune system via a complex network, which includes lymph nodes, vessels, and lymphocytes. With the deepening understanding of tumor immunology, a plethora of immunotherapies, which include vaccines, photothermal therapy, and photodynamic therapy, have been established for antitumor treatments. However, the deleterious off-target effects and nonspecific targeting of therapeutic agents result in low efficacy of immunotherapy. Fortunately, nanoparticle-based approaches for targeting the lymphatic system afford a unique opportunity to manufacture drugs that can simultaneously tackle both aspects, thereby improving tumor treatments. Over the past decades, great strides have been made in the development of DC vaccines and nanomedicine as antitumor treatments in the field of lymphatic therapeutics and diagnosis. In this review, we summarize the current strategies through which nanoparticle technology has been designed to target the lymphatic system and describe applications of lymphatic imaging for the diagnosis and image-guided surgery of tumor metastasis. Moreover, improvements in the tumor specificity of nanovaccines and medicines, which have been realized through targeting or stimulating the lymphatic system, can provide amplified antitumor immune responses and reduce side effects, thereby promoting the paradigm of antitumor treatment into the clinic to benefit patients.


Assuntos
Antineoplásicos/farmacologia , Imunoterapia/métodos , Sistema Linfático/imunologia , Nanomedicina , Nanopartículas/administração & dosagem , Neoplasias/tratamento farmacológico , Animais , Humanos , Sistema Linfático/efeitos dos fármacos , Nanopartículas/química , Neoplasias/imunologia
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