Solid lipid nanoparticles as intracellular drug transporters: An investigation of the uptake mechanism and pathway

Martins, Susana; Lima, Sofia A. Costa; Carneiro, Teiliane Rodrigues; Cordeiro-da-Silva, Anabela; Souto, Eliana B.; Ferreira, Domingos

doi:10.1016/j.ijpharm.2012.03.032

Cited by 145 publications

(77 citation statements)

References 42 publications

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“…The data of this study showed that Tween-80 as oil phase surfactant could increase the EA encapsulation. The size of nanoparticles used in a drug delivery system should be large enough (> 30 nm) to prevent their elimination by renal excretion, but small enough (up to 200 nm) to escape rapidly taken up by the mononuclear phagocyte system cells (24). Kind and concentration of emulsifier have significant effect in particle size.…”

Section: Discussionmentioning

confidence: 99%

Enhanced Anti-Cancer Capability of Ellagic Acid Using Solid Lipid Nanoparticles (SLNs)

et al. 2018

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Background: Ellagic acid (EA) is a polyphenol, whose anti-cancer properties have been demonstrated in several cancer studies, but the poor water solubility and low bioavailability have limited its therapeutic potential. Objectives: The present study proposed to develop solid lipid nanoparticles (SLNs) as a delivery system for improving the anticancer capability of EA on prostate cancer cell line. Methods: EA-loaded SLNs were prepared by hot homogenization technique and characterized by different techniques. Cytotoxicity of EA and EA-loaded SLNs on prostate cancer cell line (PC3) was evaluated by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, and nucleus condensation, or chromatin fragmentation (the signs of apoptosis) were studied by 4'-6-diamidino-2-phenylindole (DAPI) staining. The expression of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax), which are involved in apoptosis, were evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results:The nanoparticles with appropriate characteristics (particle size of 96 nm and Encapsulation Efficiency of 88%) were prepared. The in vitro drug release profile showed a burst release in the first hours and followed by a sustained EA release until 72 hours. EA-loaded SLNs displayed a good stability for 4 weeks of storage at 4 -8°C. Cytotoxicity evaluations demonstrated that EA-loaded SLNs prevented prostate cancer cells growth in a low IC50 value compared to the EA. The results of qRT-PCR demonstrated that EA causes up-regulation of Bax and this regulation intensified when EA was loaded into SLNs, but there was no punctual correlation between the EA and EA-loaded SLNs in down-regulation of Bcl-2. Conclusions:The results strengthen our hope that loading EA into SLNs could possibly overcome the therapeutic limitations of EA and make it more effective in prostate cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Enhanced Anti-Cancer Capability of Ellagic Acid Using Solid Lipid Nanoparticles (SLNs)

et al. 2018

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“…45 Shimoni et al investigaram a internalização de nano-cápsulas de hidrogel de ácido polimetacrílico em células HeLa, concluindo que cápsulas esféricas eram internalizadas em maior quantidade que outras com mesma composição, mas com formato alongado. 46 Martins et al demonstraram que nanopartículas lipídicas sólidas apresentavam taxa de internalização preferencial em linhagens de glioma humano (A172 e U87) em relação à macrófagos, fato que aumenta a relevância dessas nanopartículas como carreadores de fármacos anti-neoplási-cos. 47 Silva et al empregaram nanopartículas poliméricas para carrear siRNA em protoplastos de tabaco BY-2 e demonstraram que esse processo depende do tempo e da concentração. 32 Esses são apenas alguns exemplos da aplicação da citometria de fluxo para estudar a internalização de nanomateriais em células eucarióticas.…”

Section: Citometria De Fluxounclassified

Como estudar interações entre nanopartículas e sistemas biológicos

et al. 2016

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Recebido em 02/05/2016; aceito em 15/06/2016; publicado na web em 16/08/2016 STUDYING THE INTERACTIONS BETWEEN NANOPARTICLES AND BIOLOGICAL SYSTEMS. Although in recent years there has been an increasing amount of literature on nanotechnology and their clinical applications, it is still scarce a deep understanding of the interactions at the molecular levels between nanoparticles and cells. Studies demonstrating the underlying mechanisms of nanoparticles endocytosis, intracellular trafficking, and cellular processing are imperative to understand better how cells interact with those materials and their possible undesired effects, e.g. nanotoxicity. The rising awareness concerning nanoparticles applications and its interactions with the cellular environment is part of the new research field called Nanotoxicology. The cumulative knowledge in nanotoxicology will allow us to foresee toxic effects, establish regulations and limits for nanoparticles applications. In this work, we discuss the theoretical concepts about studying endocytosis and intracellular trafficking of nanoparticles. The nanoparticles-cell interactions are a multi-step process, which can be divided into nanoparticles' internalization, intracellular processing and triggering effects of nanomaterials on eukaryotic cells. Finally, we discuss the main techniques used to study this process: flow cytometry, use of endocytosis inhibitors and confocal microscopy.Keywords: endocytosis; intracellular trafficking; nanoparticles, nanotoxicology; nano-cell interactions. INTRODUÇÃONanotecnologia é um dos ramos mais promissores de tecnologia, sobre o qual se deposita grandes expectativas. 1 Somente em 2015, foram publicados cerca de 9400 artigos relacionados ao termo "Nanotechnology" no banco de dados Science Direct; além disso, diversos produtos têm sido testados e comercializados, por exemplo, protetores solares, cosméticos, produtos biomédicos, biosensores e sistemas para transporte e entrega de fármacos. 2 Entretanto, há uma crescente preocupação com a segurança e possíveis efeitos nocivos de nanomateriais que vêm sendo desenvolvidos, 3 pois dados e regulamentações internacionais referentes à segurança e uso desses materiais ainda são escassos, ainda estão em debate ou em fase de implementação. 4 Uma nova área da ciência destinada ao estudo de efeitos adversos de nanomateriais foi recentemente criada, a Nanotoxicologia. 5 O conhecimento acumulado nessa área tem como objetivo prever efeitos tóxicos e auxiliar nas regulamentações e diretrizes para aplicação da nanotecnologia 6 e uso de produtos a ela relacionados. A Figura 1 mostra o crescimento do número de artigos científicos que contêm o termo "nanotoxicology" e estão no banco de dados do National Center for Biotechnology Information (NCBI), subdivisão do National Institute of Health (NIH/USA).Apesar do número de artigos em nanotoxicologia ser crescente, esta é uma área ainda muito recente (com menos de uma década), e ainda não é possível determinar exatamente quais impactos os sistemas naturais e artificiais co...

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“…This concept also makes drug uptake independent of transporters by nanoparticle endocytosis into the targeted cells. 16 Nanoparticulate carriers are introduced for passive drug targeting to tumor tissues through the enhanced permeability and retention (EPR) effect. [17][18][19] EPR implies that nanoparticles tend to accumulate in tumor tissue much more than they do in normal tissue.…”

Section: -Azacytidine Was First Synthesized In 1963mentioning

confidence: 99%

“…It was claimed that the appropriate size range for the effective cytotoxic performance of nanoparticles is <200 nm. 16 Therefore, most formulations in this study were in the suitable size range. The PDI of SLNs was found to be in the range of 0.18 to 0.31 ( Table 1).…”

Section: Sln Preparationmentioning

confidence: 99%

Enhanced in Vitro Anti-Tumor Activity of 5-Azacytidine by Entrapment into Solid Lipid Nanoparticles

Jahanfar¹,

Hasani²,

Shanebandi³

et al. 2016

Adv Pharm Bull

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Solid lipid nanoparticles as intracellular drug transporters: An investigation of the uptake mechanism and pathway

Cited by 145 publications

References 42 publications

Enhanced Anti-Cancer Capability of Ellagic Acid Using Solid Lipid Nanoparticles (SLNs)

Enhanced Anti-Cancer Capability of Ellagic Acid Using Solid Lipid Nanoparticles (SLNs)

Como estudar interações entre nanopartículas e sistemas biológicos

Enhanced in Vitro Anti-Tumor Activity of 5-Azacytidine by Entrapment into Solid Lipid Nanoparticles

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