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1.
PLoS One ; 15(2): e0228463, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32027689

RESUMO

Infection with Brucella abortus causes contagious zoonosis, brucellosis, and leads to abortion in animals and chronic illness in humans. Chitosan nanoparticles (CNs), biocompatible and nontoxic polymers, acts as a mucosal adjuvant. In our previous study, B. abortus malate dehydrogenase (Mdh) was loaded in CNs, and it induced high production of pro-inflammatory cytokines in THP-1 cells and systemic IgA in BALB/C mice. In this study, the time-series gene expression analysis of nasal-associated lymphoid tissue (NALT) was performed to identify the mechanism by which Mdh affect the target site of nasal immunization. We showed that intranasal immunization of CNs-Mdh reduced cell viability of epithelial cells and muscle cells at first 1 h, then induced cellular movement of immune cells such as granulocytes, neutrophils and lymphocytes at 6h, and activated IL-6 signaling pathway at 12h within NALT. These activation of immune cells also promoted signaling pathway for high-mobility group box 1 protein (HMGB1), followed by the maturation of DCs required for mucosal immunity. The CNs also triggered the response to other organism and inflammatory response, showing it is immune-enhancing adjuvant. The ELISA showed that significant production of specific IgA was detected in the fecal excretions and genital secretions from the CNs-Mdh-immunized group after 2 weeks-post immunization. Collectively, these results suggest that B. abortus Mdh-loaded CNs triggers activation of HMGB1, IL-6 and DCs maturation signaling within NALT and induce production of systemic IgG and IgA.


Assuntos
Formação de Anticorpos/fisiologia , Brucella abortus/imunologia , Brucelose/prevenção & controle , Imunização/métodos , Tecido Linfoide/imunologia , Malato Desidrogenase/imunologia , Administração Intranasal , Animais , Formação de Anticorpos/efeitos dos fármacos , Brucella abortus/metabolismo , Brucelose/imunologia , Quitosana/administração & dosagem , Quitosana/química , Quitosana/imunologia , Quitosana/farmacologia , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Feminino , Imunidade nas Mucosas/efeitos dos fármacos , Imunogenicidade da Vacina , Tecido Linfoide/efeitos dos fármacos , Malato Desidrogenase/administração & dosagem , Malato Desidrogenase/metabolismo , Malato Desidrogenase/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/administração & dosagem , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/imunologia
2.
Int J Nanomedicine ; 15: 151-167, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32021171

RESUMO

Purpose: Combination therapy for tumors is an important and promising strategy to improve therapeutic efficiency. This study aims at combining tumor targeting, chemo-, and photodynamic therapies to improve the anti-tumor performance. Patients and Methods: Human serum albumin (HSA), as a nontoxic and biodegradable drug carrier, was used to load hydrophobic photosensitizers (mono-substituted ß-4-pyridyloxy phthalocyanine zinc, mPPZ) by a dilution-incubation-purification (DIP) strategy to form molecular complex HSA:mPPZ. This complex was cross-linked as nanoparticles, and then chemotherapy drug doxorubicin (DOX) was adsorbed into the nanoparticles to achieve combined photodynamic therapy and chemotherapy. Next, the surface of the obtained composite was modified by a tumor surface receptor (urokinase receptor) targeting agent (ATF-HSA) using a noncovalent method to obtain the final product (ATF-HSA@HSA:mPPZ:DOX nanoparticles, AHmDN). Results: AHmDN exhibited strong stability, remarkable cytotoxicity and higher uptake to tumor cells. Cell imaging analysis indicated that DOX was separated from AHmDN and uniformly distributed in cell nucleus while mPPZ localized in cytoplasm. The PDT activity of all the samples had been confirmed by the detection of intracellular ROS. In animal experiments, AHmDN was demonstrated to have a prominent tumor-targeting effect using a 3D imaging system. In addition, the enhanced antitumor effect of AHmDN in tumor-bearing mice was also been observed. Importantly, the tumor-targeting effect of such nanoparticles lasted for about 14 days after one injection. Conclusion: These albumin nanoparticles with combined functions of tumor targeting, chemotherapy and photodynamic therapy can highly enhance the anti-tumor effect. This drug delivery system can be applied to package other hydrophobic photosensitizers and chemotherapy drugs for improving therapeutic efficacy to tumors.


Assuntos
Doxorrubicina/administração & dosagem , Portadores de Fármacos/administração & dosagem , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Citoplasma/efeitos dos fármacos , Doxorrubicina/farmacocinética , Portadores de Fármacos/química , Feminino , Humanos , Neoplasias Hepáticas Experimentais/diagnóstico por imagem , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Camundongos , Nanopartículas/química , Neoplasias/tratamento farmacológico , Paclitaxel/administração & dosagem , Paclitaxel/farmacocinética , Fármacos Fotossensibilizantes/química , Espécies Reativas de Oxigênio/metabolismo , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/metabolismo , Albumina Sérica Humana/química
3.
Int J Nanomedicine ; 15: 301-313, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32021181

RESUMO

Purpose: Multifunctional drug delivery systems (DDS) are emerging as a new strategy to highly treat malignant tumors. The aim of this study is to develop a drug dual-carriers delivery system (DDDS) using the natural protein ferritin (FRT) and a nanoscale graphene oxide (NGO) as dual-carriers. Methods: The FRT is a pH-sensitive hollow cage protein with disassembly and reassembly properties and the NGO has a large surface area and a photothermal effect by which it can load and release drugs under near-infrared irradiation (NIR). Due to these unique features, the NGO loaded the anticancer drug resveratrol (RSV) and the conjugated mitochondrion targeted molecule IR780 as IR780-NGO-RSV (INR), the first drug delivery platform. Next, the INR was capsulated by FRT to form the DDDS INR@FRT which was applied for synergistic photothermal-chemotherapy of ovarian cancer. Results: Through a series of characterizations, INR@FRT showed a uniform nanosphere structure and remarkable stability in physiological condition. Heat/pH 5.0 was confirmed to trigger RSV release from the INR@FRT. After taken up by cells, INR@FRT located to the lysosomes where the acidic environment triggered INR release. INR targeted the mitochondrion and released RSV to directly react with organelles, which in turn decreased the mitochondrion membrane potential and caused cell apoptosis. In-vivo experiments showed that INR@FRT combined with NIR irradiation displayed remarkable tumor suppression with a high survival rate after 60 days of treatment. Finally, the biocompatibility of INR@FRT was demonstrated in vitro and in vivo. Conclusion: These results highlight the immense potential of INR@FRT as a type of DDDS for the treatment of tumors.


Assuntos
Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Indóis/farmacologia , Mitocôndrias/efeitos dos fármacos , Nanoestruturas/química , Neoplasias Ovarianas/tratamento farmacológico , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Liberação Controlada de Fármacos , Feminino , Ferritinas/química , Grafite/química , Temperatura Alta , Humanos , Concentração de Íons de Hidrogênio , Indóis/administração & dosagem , Indóis/química , Raios Infravermelhos , Camundongos Nus , Nanoestruturas/administração & dosagem , Resveratrol/administração & dosagem , Resveratrol/farmacocinética , Ensaios Antitumorais Modelo de Xenoenxerto
4.
J Nanobiotechnology ; 18(1): 14, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941495

RESUMO

BACKGROUND: In orthopedics, the treatment of implant-associated infections represents a high challenge. Especially, potent antibacterial effects at implant surfaces can only be achieved by the use of high doses of antibiotics, and still often fail. Drug-loaded magnetic nanoparticles are very promising for local selective therapy, enabling lower systemic antibiotic doses and reducing adverse side effects. The idea of the following study was the local accumulation of such nanoparticles by an externally applied magnetic field combined with a magnetizable implant. The examination of the biodistribution of the nanoparticles, their effective accumulation at the implant and possible adverse side effects were the focus. In a BALB/c mouse model (n = 50) ferritic steel 1.4521 and Ti90Al6V4 (control) implants were inserted subcutaneously at the hindlimbs. Afterwards, magnetic nanoporous silica nanoparticles (MNPSNPs), modified with rhodamine B isothiocyanate and polyethylene glycol-silane (PEG), were administered intravenously. Directly/1/7/21/42 day(s) after subsequent application of a magnetic field gradient produced by an electromagnet, the nanoparticle biodistribution was evaluated by smear samples, histology and multiphoton microscopy of organs. Additionally, a pathohistological examination was performed. Accumulation on and around implants was evaluated by droplet samples and histology. RESULTS: Clinical and histological examinations showed no MNPSNP-associated changes in mice at all investigated time points. Although PEGylated, MNPSNPs were mainly trapped in lung, liver, and spleen. Over time, they showed two distributional patterns: early significant drops in blood, lung, and kidney and slow decreases in liver and spleen. The accumulation of MNPSNPs on the magnetizable implant and in its area was very low with no significant differences towards the control. CONCLUSION: Despite massive nanoparticle capture by the mononuclear phagocyte system, no significant pathomorphological alterations were found in affected organs. This shows good biocompatibility of MNPSNPs after intravenous administration. The organ uptake led to insufficient availability of MNPSNPs in the implant region. For that reason, among others, the nanoparticles did not achieve targeted accumulation in the desired way, manifesting future research need. However, with different conditions and dimensions in humans and further modifications of the nanoparticles, this principle should enable reaching magnetizable implant surfaces at any time in any body region for a therapeutic reason.


Assuntos
Portadores de Fármacos/química , Compostos Férricos/química , Nanopartículas de Magnetita/química , Próteses e Implantes , Dióxido de Silício/química , Animais , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/toxicidade , Feminino , Corantes Fluorescentes/química , Membro Posterior , Nanopartículas de Magnetita/toxicidade , Camundongos Endogâmicos BALB C , Ortopedia , Polietilenoglicóis/química , Porosidade , Rodaminas/química , Silanos/química , Distribuição Tecidual
5.
PLoS One ; 15(1): e0228055, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31945121

RESUMO

Pneumococcal Surface Protein A (PspA) has been successfully tested as vaccine candidate against Streptococcus pneumoniae infections. Vaccines able to induce PspA-specific antibodies and Th1 cytokines usually provide protection in mice. We have shown that the whole cell pertussis vaccine (wP) or components from acellular pertussis vaccines, such as Pertussis Toxin or Filamentous Hemagglutinin (FHA), are good adjuvants to PspA, suggesting that combined pertussis-PspA vaccines would be interesting strategies against the two infections. Here, we evaluated the potential of wP as a delivery vector to PspA. Bordetella pertussis strains producing a PspA from clade 4 (PspA4Pro) fused to the N-terminal region of FHA (Fha44) were constructed and inactivated with formaldehyde for the production of wPPspA4Pro. Subcutaneous immunization of mice with wPPspA4Pro induced low levels of anti-PspA4 IgG, even after 3 doses, and did not protect against a lethal pneumococcal challenge. Prime-boost strategies using wPPspA4Pro and PspA4Pro showed that there was no advantage in using the wPPspA4Pro vaccine. Immunization of mice with purified PspA4Pro induced higher levels of antibodies and protection against pneumococcal infection than the prime-boost strategies. Finally, purified Fha44:PspA4Pro induced high levels of anti-PspA4Pro IgG, but no protection, suggesting that the antibodies induced by the fusion protein were not directed to protective epitopes.


Assuntos
Adesinas Bacterianas/administração & dosagem , Adjuvantes Imunológicos/administração & dosagem , Proteínas de Bactérias/farmacologia , Vacina contra Coqueluche/administração & dosagem , Infecções Pneumocócicas/prevenção & controle , Fatores de Virulência de Bordetella/administração & dosagem , Animais , Antígenos de Bactérias/farmacologia , Antígenos de Superfície/farmacologia , Portadores de Fármacos/administração & dosagem , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Vacinação
6.
Spectrochim Acta A Mol Biomol Spectrosc ; 224: 117392, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31330421

RESUMO

Curcumin the extract obtained from the dried rhizome of turmeric, Curcuma longa is a hydrophobic phenol that delivers numerous pharmacological actions like anti-inflammatory, anti-microbial and anti-oxidant, anti-psoriasis, antidiabetic, anticancer. But curcumin has low bioavailability issues that accompany low aqueous solubility, further, when administered orally, >90% of the drug degrades rapidly in the alkaline medium. Administering the drug topically can bypass the problem as well as first-pass metabolism and therefore delivering the drug at the targeted site of action. Encapsulating curcumin in nanostructured lipid nanocarriers (NLC) is an excellent novel strategy. Further, these NLC provides both the controlled release and helps in the enhanced permeation of the drug through the skin's physiological barrier, stratum corneum. For the NLC characterization, a reliable method must be developed that can accurately and precisely determine the drug content in the formulation and also for its in-vitro and ex-vivo characterization. This experiment describes the analytical validation parameters described as per International Conference of Harmonization guidelines to develop a method using the UV-Visible spectroscopy. The method was developed in two solvent systems i.e. methanol and 6.4 pH phosphate buffer with 1.5% polysorbate 80. Methanol solvent was used for the determination of curcumin in the NLC formulation via determining the encapsulation efficiency and 6.4 pH phosphate buffer with 1.5% polysorbate 80 solvent was used for in-vitro and ex-vivo characterization of the developed NLC formulation (cream and gel). These methods were validated in response to linearity, the limit of detection, the limit of quantification, precision, accuracy, repeatability, and specificity.


Assuntos
Curcumina/química , Portadores de Fármacos/química , Lipídeos/química , Nanoestruturas/química , Espectrofotometria Ultravioleta/métodos , Administração Tópica , Animais , Curcumina/administração & dosagem , Curcumina/farmacocinética , Portadores de Fármacos/administração & dosagem , Cabras , Limite de Detecção , Modelos Lineares , Reprodutibilidade dos Testes , Pele/química , Pele/metabolismo
7.
Food Chem ; 302: 125328, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31404868

RESUMO

To control the oral bioavailability of curcumin, we fabricated solid lipid nanoparticles (SLNs) using tristearin and polyethylene glycol (PEG)ylated emulsifiers. Lipolysis of prepared SLNs via simulated gastrointestinal digestion was modulated by altering the types and concentrations of emulsifiers. After digestion, the size/surface charge of micelles formed from SLN digesta were predictable and >91% of curcumin was bioaccessible in all of the SLNs. The curcumin permeation rate through mucus-covered gut epithelium in vitro was dependent on the size/surface charge of the micelles. Curcumin loaded in long-PEGylated SLNs rapidly permeated the epithelium due to the neutral surface charge of the micelles, resulting in a >12.0-fold increase in bioavailability compared to curcumin solution in a rat model. These results suggest that the bioavailability of curcumin can be controlled by modulating the interfacial properties of SLNs, which will facilitate the development of curcumin formulations for use in functional foods and pharmaceuticals.


Assuntos
Curcumina/administração & dosagem , Curcumina/farmacocinética , Emulsificantes/química , Nanopartículas/química , Administração Oral , Animais , Disponibilidade Biológica , Células CACO-2 , Digestão , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Humanos , Lipídeos/química , Masculino , Nanopartículas/administração & dosagem , Polietilenoglicóis/química , Ratos , Ratos Sprague-Dawley , Triglicerídeos/química
8.
Int J Mol Sci ; 20(24)2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31861113

RESUMO

Safe and effective delivery of therapeutics at the target site is the key to successful therapy. Nanocarriers can offer significant advantages over conventional dosage forms. Over the decades, nanoparticles have been extensively used to increase bioavailability, improve solubility and stability, reduce toxicities, and facilitate the controlled release of therapeutics. Further, nanoparticles have often been surface-functionalized with a variety of ligands to enhance circulation half-life and increase target-specificity. Although nanotechnology has shown significant therapeutic benefits for multiple biomedical applications, limited nanoparticle-based formulations have progressed to clinical trials, and only a few have reached the pharmaceutical market. This editorial is an introduction to the special issue entitled Surface-Functionalized Nanoparticles as Drug Carriers. We outline the scope of the special issue, summarize the results and conclusions of the nine articles published in this issue, and provide perspective on the application of surface-functionalized nanoparticles in the drug delivery field.


Assuntos
Preparações de Ação Retardada/administração & dosagem , Portadores de Fármacos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/administração & dosagem , Nanotecnologia/métodos , Disponibilidade Biológica , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Portadores de Fármacos/química , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Humanos , Nanopartículas/química
9.
Crit Rev Ther Drug Carrier Syst ; 36(4): 277-304, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679189

RESUMO

Dendrimers, commonly referred to as arborols, offer tremendous opportunities for drug delivery, diagnostics, and treatment applications. This may be attributed to the characteristic features of their three architectural components: core, branches, and terminal groups. These components provide vast flexibility to designers. They act as highly moldable platforms that can be modified to suit the needs of application designers. Effectively, the type, length, and molecular weight of the core, branches and terminal groups may be customized to achieve desired characteristics and satisfy the demands of numerous applications. These perfectly designed multifunctional structures are reviewed in the current paper, focusing on their complex archetypical design for interphase applications; novel drug delivery applications, especially oral, ocular, pulmonary, transdermal; targeted, and controlled-release; and diagnosis and treatment of diseases like cancer, diabetes, and autoimmune disorders.


Assuntos
Dendrímeros/administração & dosagem , Dendrímeros/química , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Animais , Preparações de Ação Retardada , Humanos , Terapia de Alvo Molecular
10.
Crit Rev Ther Drug Carrier Syst ; 36(3): 239-276, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679248

RESUMO

Pulmonary tuberculosis (TB) is a leading cause of death worldwide and is caused by the pathogen Mycobacterium tuberculosis (MTb). As treatment for TB, dry powders for inhalation (DPIs) are considered stable compared with nebulizers and metered dose inhalers and are suitable for high-dose formulations. Although extensive research has been done over the last two to three decades on nanocarrier-based DPIs for targeting MTb infection, none of the anti-TB DPI formulations have reached the market. Challenges in the proper assessment of nanocarrier-based DPIs due to the complexity of lungs is one of the reasons. In this review, the details of in vitro evaluation parameters of nanocarriers and nanocarrier-based DPIs along with their need and basic principles are discussed. Further, the thorough in vitro, ex vivo, and in vivo pharmacological evaluations, together with their procedures wherever required, are covered. The different evaluation parameters during process development, release specifications, and stability studies suggested by U.S. Food and Drug Administration Center for Drug Evaluation and Research to apply for new drug applications and abbreviated new drug applications of DPIs are also discussed. Lastly, the evaluation parameters for DPIs provided in European, United States, British, and Indian pharmacopeias are summarized.


Assuntos
Antituberculosos/administração & dosagem , Portadores de Fármacos/administração & dosagem , Mycobacterium tuberculosis/efeitos dos fármacos , Nanopartículas/administração & dosagem , Tuberculose Pulmonar/tratamento farmacológico , Administração por Inalação , Animais , Antituberculosos/química , Portadores de Fármacos/química , Inaladores de Pó Seco , Humanos , Nanopartículas/química , Pós/administração & dosagem , Pós/química , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Nat Commun ; 10(1): 4520, 2019 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-31586045

RESUMO

Control over the protein corona of nanomaterials allows them to function better. Here, by taking graphene/gold as examples, we comprehensively assessed the association of surface properties with the protein corona. As revealed by in vitro measurements and computations, the interaction between graphene/gold and HSA/IgE was inversely correlated with the hydroxyl group availability, whereas the interaction between that and ApoE was comparatively less relevant. Molecular simulations revealed that the number and the distribution of surface hydroxyl groups could regulate the manner in which nanomaterials interact with proteins. Moreover, we validated that ApoE pre-adsorption before injection enhances the blood circulation of nanomaterials relative to their pristine and IgE-coated counterparts. This benefit can be attributed to the invulnerability of the complementary system provided by ApoE, whose encasement does not increase cytotoxicity. Overall, this study offers a robust yet simple way to create protein corona enriched in dysopsonins to realize better delivery efficacy.


Assuntos
Portadores de Fármacos/química , Nanopartículas/química , Coroa de Proteína/metabolismo , Adsorção , Animais , Apolipoproteínas E/química , Apolipoproteínas E/metabolismo , Linhagem Celular Tumoral/transplante , Modelos Animais de Doenças , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/farmacocinética , Feminino , Ouro/química , Grafite/química , Humanos , Imunoglobulina E/química , Imunoglobulina E/metabolismo , Injeções Intravenosas , Camundongos , Simulação de Dinâmica Molecular , Nanopartículas/metabolismo , Neoplasias/tratamento farmacológico , Proteínas Opsonizantes/química , Ligação Proteica , Coroa de Proteína/química , Estrutura Secundária de Proteína , Células RAW 264.7 , Albumina Sérica Humana/metabolismo , Propriedades de Superfície
12.
J Enzyme Inhib Med Chem ; 34(1): 1590-1596, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31581863

RESUMO

Oral colon administration system has become a new method to treat intestinal diseases. The implementation of colon drug delivery system is restricted by many aspects, including physical and chemical properties, drug delivery mode, gastrointestinal physiological factors, and so on. Delivery methods to overcome these challenges revolve around the mechanisms of drug delivery, including the use of rational dosage forms to avoid the complex pH environment, and the prevention of drug release and absorption in the upper digestive tract.


Assuntos
Colo , Portadores de Fármacos/química , Administração Oral , Animais , Colo/metabolismo , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Portadores de Fármacos/administração & dosagem , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Microbioma Gastrointestinal , Humanos , Concentração de Íons de Hidrogênio , Enteropatias/tratamento farmacológico , Polímeros/química
13.
Int J Nanomedicine ; 14: 6407-6424, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31496694

RESUMO

Chagas disease is one of the most important public health problems in Latin America due to its high mortality and morbidity levels. There is no effective treatment for this disease since drugs are usually toxic with low bioavailability. Serious efforts to achieve disease control and eventual eradication have been unsuccessful to date, emphasizing the need for rapid diagnosis, drug development, and a reliable vaccine. Novel systems for drug and vaccine administration based on nanocarriers represent a promising avenue for Chagas disease treatment. Nanoparticulate systems can reduce toxicity, and increase the efficacy and bioavailability of active compounds by prolonging release, and therefore improve the therapeutic index. Moreover, nanoparticles are able to interact with the host's immune system, modulating the immune response to favour the elimination of pathogenic microorganisms. In addition, new advances in diagnostic assays, such as nanobiosensors, are beneficial in that they enable precise identification of the pathogen. In this review, we provide an overview of the strategies and nanocarrier-based delivery systems for antichagasic agents, such as liposomes, micelles, nanoemulsions, polymeric and non-polymeric nanoparticles. We address recent progress, with a particular focus on the advances of nanovaccines and nanodiagnostics, exploring new perspectives on Chagas disease treatment.


Assuntos
Doença de Chagas/tratamento farmacológico , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Portadores de Fármacos/administração & dosagem , Humanos , Micelas , Nanopartículas/administração & dosagem , Polímeros/química
14.
Int J Nanomedicine ; 14: 6539-6553, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31496699

RESUMO

Aim: This paper reports on the incorporation of oleic acid (OA) within nanostructured lipid carriers (OA-NLC) to improve the anti-inflammatory effects in the presence of albumin. Materials and methods: NLCs produced via hot high-shear homogenization/ultrasonication were characterized in terms of particle size, zeta potential, and toxicity. We examined the effects of OA-NLC on neutrophil activities. Dermatologic therapeutic potential was also elucidated by using a murine model of leukotriene B4-induced skin inflammation. Results: In the presence of albumin, OA-NLC but not free OA inhibited superoxide generation and elastase release. Topical administration of OA-NLC alleviated neutrophil infiltration and severity of skin inflammation. Conclusion: OA incorporated within NLC can overcome the interference of albumin, which would undermine the anti-inflammatory effects of OA. OA-NLC has potential therapeutic effects in topical ointments.


Assuntos
Portadores de Fármacos/química , Inflamação/patologia , Lipídeos/química , Nanoestruturas/química , Neutrófilos/fisiologia , Ácido Oleico/química , Soroalbumina Bovina/farmacologia , Pele/patologia , Administração Tópica , Adulto , Animais , Cálcio/metabolismo , Bovinos , Morte Celular/efeitos dos fármacos , Portadores de Fármacos/administração & dosagem , Humanos , Leucotrieno B4 , Lipídeos/toxicidade , Masculino , Camundongos Endogâmicos BALB C , Nanoestruturas/administração & dosagem , Nanoestruturas/toxicidade , Nanoestruturas/ultraestrutura , Ativação de Neutrófilo/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Ácido Oleico/toxicidade , Elastase Pancreática/metabolismo , Superóxidos/metabolismo , Adulto Jovem
16.
Biol Pharm Bull ; 42(8): 1376-1383, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31366872

RESUMO

High-density lipoprotein (HDL) particles that are formed in vivo adopt a disk-shaped structure, in which the periphery of the discoidal phospholipid bilayer is surrounded by apolipoprotein. Such discoidal nanoparticles can be reconstituted with certain apolipoproteins and phospholipids and are commonly called lipid nanodisks. Apolipoprotein E (apoE), one of the HDL constituent proteins, serves as a ligand for the low-density lipoprotein (LDL) receptor. Thus, it is considered that biocompatible delivery vehicles targeting LDL receptors could be prepared by incorporating apoE as the protein component of lipid nanodisks. To enhance targeting efficiency, we designed lipid nanodisks with a large number of ligands using a peptide with the LDL receptor-binding region of apoE combined with a high lipid affinity sequence (LpA peptide). In our study, the LpA peptide spontaneously formed discoidal complexes (LpA nanodisks) of approximately 10 nm in size, equivalent to native HDL. LpA peptides on nanodisks adopted highly α-helical structures, a competent conformation capable of interacting with LDL receptors. As anticipated, the uptake of LpA nanodisks into LDL receptor-expressing cells (HepG2) was higher than that of apoE nanodisks, suggesting an enhanced targeting efficiency via the enrichment of LDL receptor-binding regions on the particle. Biodistribution studies using 111In-labeled LpA nanodisks showed little splenic accumulation and prolonged retention in blood circulation, reflecting the biocompatibility of LpA nanodisks. High accumulation of 111In-labeled LpA nanodisks was observed in the liver as well as in implanted tumors, which abundantly express LDL receptors. Thus, LpA nanodisks are potential biocompatible delivery vehicles targeting LDL receptors.


Assuntos
Apolipoproteínas E , Dimiristoilfosfatidilcolina/administração & dosagem , Portadores de Fármacos/administração & dosagem , Nanoestruturas/administração & dosagem , Peptídeos/administração & dosagem , Receptores de LDL/metabolismo , Animais , Dimiristoilfosfatidilcolina/farmacocinética , Portadores de Fármacos/farmacocinética , Células Hep G2 , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Peptídeos/farmacocinética , Distribuição Tecidual
17.
Biomater Sci ; 7(10): 3942-3960, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31414096

RESUMO

Calcium phosphate (CaP) was engineered as a drug delivery nanocarrier nearly 50 years ago due to its biocompatibility and biodegradability. In recent years, several approaches have been developed for the preparation of size-controllable, stable and multifunctional CaP nanocarriers, and several targeting moieties have also been decorated on the surface of these nanocarriers for active targeting. The CaP nanocarriers have been utilized for loading probes, nucleic acids, anticancer drugs and photosensitizers for cancer imaging, therapy and theranostics. Herein, we reviewed the recent advances in the preparation strategies of CaP nanocarriers and the applications of these nanocarriers in tumor diagnosis, gene delivery, drug delivery and theranostics and finally provided perspectives.


Assuntos
Antineoplásicos/administração & dosagem , Fosfatos de Cálcio/administração & dosagem , Portadores de Fármacos/administração & dosagem , Nanopartículas/administração & dosagem , Neoplasias/terapia , Animais , Fosfatos de Cálcio/química , Portadores de Fármacos/química , Técnicas de Transferência de Genes , Humanos , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Nanomedicina Teranóstica
18.
Int J Pharm ; 569: 118624, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31419461

RESUMO

Nanostructured lipid carriers (NLC) and nanoemulsions (NE) are colloid carriers which could improve dermal delivery of tacrolimus. The aims of this study were to evaluate effects of different formulation and process parameters on physicochemical characteristics and stability of lecithin-based NLC with glyceryl palmitostearate as solid and propylene glycol monocaprylate as liquid lipid and to compare the influence of different inner structure of tacrolimus-loaded NLC and corresponding NE on physicochemical characteristics, stability, entrapment efficiency, in vitro drug release and overall skin performance. Solid/liquid lipid ratio, total amount of lipids, homogenization pressure and cooling after the preparation were identified as critical variables in NLC development. Moreover, tacrolimus-loaded NLC emerged as more stabile carrier than NE. Differential stripping performed on porcine ear skin revealed significantly higher tacrolimus amount in stratum corneum from nanocarriers compared to referent ointment (Protopic®). Similarly the highest amount of tacrolimus in hair follicles was obtained using NLC (268.54 ±â€¯92.38 ng/cm2), followed by NE (128.17 ±â€¯48.87 ng/cm2) and Protopic® (77.61 ±â€¯43.25 ng/cm2). Contrary, the highest permeation rate through full-thickness porcine ear skin was observed for Protopic®, implying that the selection of experimental setup is critical for reliable skin performance assessment. Overall, developed NLC could be suggested as promising carrier in a form of lotion for tacrolimus dermal delivery.


Assuntos
Portadores de Fármacos/administração & dosagem , Imunossupressores/administração & dosagem , Lecitinas/administração & dosagem , Nanoestruturas/administração & dosagem , Tacrolimo/administração & dosagem , Administração Cutânea , Animais , Caprilatos/administração & dosagem , Caprilatos/química , Portadores de Fármacos/química , Composição de Medicamentos , Liberação Controlada de Fármacos , Emulsões , Imunossupressores/química , Lecitinas/química , Lipídeos/administração & dosagem , Lipídeos/química , Nanoestruturas/química , Pomadas , Propilenoglicóis/administração & dosagem , Propilenoglicóis/química , Pele/metabolismo , Absorção Cutânea , Suínos , Tacrolimo/química
19.
Eur J Pharm Sci ; 139: 105043, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31415903

RESUMO

Amorphous solid dispersion stands out among different formulation strategies for the improvement of dissolution rate and bioavailability via generating supersaturated drug solution, which provides a higher solubility than the crystalline counterpart, leading to a promoted intestinal absorption. Soluplus (SOL), termed as the fourth generation of solid dispersion carrier, presented a preferable effect on supersaturation maintaining and bioavailability enhancement for poorly water soluble drugs. However, some binary drug/SOL systems still suffer from insufficient dissolution and unsatisfied in vivo absorption. Thus, taking Lacidipine (LCDP) as a model drug, the aim of this study was to explore a ternary amorphous solid dispersion consisted of SOL and a surfactant to further increasing the dissolution rate and in vivo absorption. First of all, various surfactants were screened via equilibrium solubility enhancement and sodium dodecyl sulfate (SDS) was selected as the most effective candidate. Thereafter, the influence of SOL/SDS and drug/carrier weight ratio on the supersaturation maintaining was investigated. The supersaturated drug solutions were spray dried and the in vitro release, pharmacokinetic behavior as well as physical stability were investigated. It was found that although combination use of SOL and SDS did not present remarkable advantage in supersaturation maintenance in liquid state, 6-7 times higher dissolution rate under non-sink condition was noticed at SOL/SDS ratio 3:1 after spray drying, for LCDP/SOL/SDS based formulation compared to that of the binary LCDP/SOL system, which was maintained even after 92.5% humidity and 60 °C accelerated stability test. Moreover, compared to the LCDP/SOL formulation, approximately 3.3 and 3.7-fold increase in C max and AUC0-∞ was achieved with LCDP/SOL/SDS based formulation. In conclusion, the presented SDS could not only be regarded as solubility enhancer but also dissolution or bioavailability promoter, highlighting its potential application in ternary supersaturable amorphous solid dispersion for further increasing the dissolution and in vivo absorption of poorly water soluble drugs.


Assuntos
Di-Hidropiridinas/administração & dosagem , Portadores de Fármacos/administração & dosagem , Excipientes/administração & dosagem , Polietilenoglicóis/administração & dosagem , Polivinil/administração & dosagem , Dodecilsulfato de Sódio/administração & dosagem , Tensoativos/administração & dosagem , Animais , Disponibilidade Biológica , Di-Hidropiridinas/química , Di-Hidropiridinas/farmacocinética , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Excipientes/química , Excipientes/farmacocinética , Absorção Intestinal/efeitos dos fármacos , Polietilenoglicóis/química , Polietilenoglicóis/farmacocinética , Polivinil/química , Polivinil/farmacocinética , Ratos Sprague-Dawley , Dodecilsulfato de Sódio/química , Dodecilsulfato de Sódio/farmacocinética , Tensoativos/química , Tensoativos/farmacocinética
20.
Curr Drug Deliv ; 16(7): 645-653, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31362675

RESUMO

BACKGROUND: Amphotericin B (AmB) is important for the treatment of systemic fungal infections. Nowadays, only intravenous administration (IV) of AmB has been available due to its low aqueous solubility. Two forms of AmB are available. The first is Fungizone®, a mixture of AmB and sodium deoxcycholate that produces severe nephrotoxicity. The second are lipid-based formulations that reduce nephrotoxicity, but they are costly and require higher dose than Fungizone®. Thus, a cheaper delivery system with reduced AmB toxicity is required. OBJECTIVE: To develop and characterize AmB loaded-nanostructured lipid carriers (AmB-loaded NLCs) for IV administration to reduce AmB toxicity. METHODS: AmB-loaded NLCs with different solid lipids were prepared by the high-pressure homogenization technique. Their physicochemical properties and the drug release profile were examined. The molecular structure of AmB, antifungal and hemolysis activities of developed AmB-loaded NLCs were also evaluated. RESULTS: AmB-loaded NLCs ~110 to ~140 nm in diameter were successfully produced with a zeta potential of ~-19 mV and entrapment efficiency of ~75%. In vitro release showed fast release characteristics. AmB-loaded NLCs could reduce the AmB molecular aggregation as evident from the absorbance ratio of the first to the fourth peak showing a partial aggregation of AmB. This result suggested that AmB-loaded NLCs could offer less nephrotoxicity compared to Fungizone®. In vitro antifungal activity of AmB-loaded NLCs showed a minimum inhibitory concentration of 0.25 µgmL-1. CONCLUSION: AmB-loaded NLCs present high potential carriers for effective IV treatment with prolonged circulation time and reduced toxicity.


Assuntos
Anfotericina B , Antifúngicos , Portadores de Fármacos , Nanoestruturas , Administração Intravenosa , Anfotericina B/administração & dosagem , Anfotericina B/química , Anfotericina B/toxicidade , Animais , Antifúngicos/administração & dosagem , Antifúngicos/química , Antifúngicos/toxicidade , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Eritrócitos/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Lipídeos/administração & dosagem , Lipídeos/química , Lipídeos/toxicidade , Nanoestruturas/administração & dosagem , Nanoestruturas/química , Nanoestruturas/toxicidade , Ovinos
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