Glutathione Reductase-Sensitive Polymeric Micelles for Controlled Drug Delivery on Arthritic Diseases

Lima, Antônio Carlos Pedroso de; Reis, Rui L.; Ferreira, Helena; Neves, Nuno M.

doi:10.1021/acsbiomaterials.1c00412

Cited by 19 publications

(12 citation statements)

References 52 publications

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“…The unreacted compounds were removed by centrifugation (30 min, 4000 rpm at 20 °C) using Vivaspin 300 kD filter units (Fisher Scientific). Micelles composed of methoxypolyethylene glycol amine (5000 kDa)–glutathione–palmitic acid (mPEG-GSH n -PA) polymers were prepared through the nanoprecipitation method . FITC (0.5 mg) was dissolved in the polymer solution in tetrahydrofuran before the micelle production.…”

Section: Methodsmentioning

confidence: 59%

“…Ch-HA NPs, mPEG-GSH n -PA micelles, and Chol/EPC/DSPE-PEG-Mal LUVs incorporating a fluorescent dye were characterized in terms of size, PDI, and ζ-potential (Table ). The results are in agreement with previous works. − Hence, all of the formulations have a size of around 115–130 nm and a PDI lower than 0.2, which indicates the homogeneity of the NP populations. Regarding the ζ-potential, Ch-HA NPs have a positive surface charge around +28 mV, while mPEG-GSH n -PA micelles and Chol/EPC/DSPE-PEG-Mal LUVs present a negative surface charge of around −26 mV.…”

Section: Resultsmentioning

confidence: 99%

“…42 All NP formulations were previously evaluated to assess their in vitro stability and cytocompatibility. 32,34,35 Accordingly, the concentration of NPs used in this study was already established as safe. Furthermore, since less than 10% of the incorporated dye leaches out from the different NPs after 24 h, these fluorescently labeled formulations are suitable for cellular internalization studies.…”

Section: ■ Discussionmentioning

confidence: 99%

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Cellular Uptake of Three Different Nanoparticles in an Inflammatory Arthritis Scenario versus Normal Conditions

et al. 2021

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Nanoparticles (NPs) have wide potential applications in the biomedical field. To promote targeted and controlled delivery of encapsulated drugs, it is fundamentally important to understand the factors regulating NP uptake by different cells. Thus, the goal of the present study is to assess the internalization rates of different NPs under normal and proinflammatory states in primary human articular chondrocytes (hACs), human umbilical vein endothelial cells (EA), and human monocytes (THP-1). Here, we compared chitosan–hyaluronic acid (Ch-HA) polymeric NPs, methoxypolyethylene glycol amine–glutathione–palmitic acid (mPEG-GSH n -PA) micelles, and cholesterol/l-α-phosphatidylcholine/DSPE-PEG-Mal (Chol/EPC/DSPE-PEG-Mal) unilamellar liposomes (LUVs). Our results reveal the importance of surface charge and chemistry in determining the levels of NP internalization. Under normal conditions, the cellular uptake was ≈30% for Ch-HA NPs and ≈100% for mPEG-GSH n -PA micelles and Chol/EPC/DSPE-PEG-Mal LUVs. A proinflammatory cell state promoted a higher uptake of the Ch-HA NPs by EA cells (93% after 24 h). Since the therapeutic efficacy of the NP-loaded cargo is dependent on trafficking routes after cellular internalization, we tested their internalization pathways. Accordingly, caveolae-mediated endocytosis or energy-independent non-endocytic pathways, which circumvent lysosomal degradation, were accomplished in hACs and EA by LUVs and in M1 polarized macrophages by micelles. The present outcomes highlight the importance of considering cellular uptake and internalization pathways by the target cell when designing functional NPs for therapeutic applications.

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Section: Methodsmentioning

confidence: 59%

Section: Resultsmentioning

confidence: 99%

Section: ■ Discussionmentioning

confidence: 99%

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Cellular Uptake of Three Different Nanoparticles in an Inflammatory Arthritis Scenario versus Normal Conditions

et al. 2021

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“…This, in turn, triggers the demand for appropriate drug carriers that can be effectively loaded with these drugs and protect them until they are administered and delivered. Although great progress has been made in the development of new drug carriers, including weak polyelectrolyte complex systems, in recent years [ 167 , 168 , 169 ], there are still systems such as water-insoluble drugs that these strategies fail to encapsulate efficiently [ 170 ].…”

Section: Gels and Vectors Based On Weak Polyelectrolytes Complexesmentioning

confidence: 99%

Weak Polyelectrolytes as Nanoarchitectonic Design Tools for Functional Materials: A Review of Recent Achievements

et al. 2022

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The ionization degree, charge density, and conformation of weak polyelectrolytes can be adjusted through adjusting the pH and ionic strength stimuli. Such polymers thus offer a range of reversible interactions, including electrostatic complexation, H-bonding, and hydrophobic interactions, which position weak polyelectrolytes as key nano-units for the design of dynamic systems with precise structures, compositions, and responses to stimuli. The purpose of this review article is to discuss recent examples of nanoarchitectonic systems and applications that use weak polyelectrolytes as smart components. Surface platforms (electrodeposited films, brushes), multilayers (coatings and capsules), processed polyelectrolyte complexes (gels and membranes), and pharmaceutical vectors from both synthetic or natural-type weak polyelectrolytes are discussed. Finally, the increasing significance of block copolymers with weak polyion blocks is discussed with respect to the design of nanovectors by micellization and film/membrane nanopatterning via phase separation.

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“…Glutathione (GSH) is a tripeptide that helps induce strong antioxidant action via reversing the damages caused by reactive oxygen species (ROS) [145]. The utilization of GSH as a ligand in drug delivery is highly productive for multidimensional diseases [146,147]. Therefore, polyethylene glycol and polypropylene sulfide block copolymer (PEG-PPS) were synthesized by Wu et al [148] through previously developed methods.…”

Section: Glutathione Nanocarriersmentioning

confidence: 99%

Amino Acids, Peptides, and Proteins: Implications for Nanotechnological Applications in Biosensing and Drug/Gene Delivery

Laraib

Arshad

et al. 2021

Nanomaterials

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Over various scientific fields in biochemistry, amino acids have been highlighted in research works. Protein, peptide- and amino acid-based drug delivery systems have proficiently transformed nanotechnology via immense flexibility in their features for attaching various drug molecules and biodegradable polymers. In this regard, novel nanostructures including carbon nanotubes, electrospun carbon nanofibers, gold nanoislands, and metal-based nanoparticles have been introduced as nanosensors for accurate detection of these organic compounds. These nanostructures can bind the biological receptor to the sensor surface and increase the surface area of the working electrode, significantly enhancing the biosensor performance. Interestingly, protein-based nanocarriers have also emerged as useful drug and gene delivery platforms. This is important since, despite recent advancements, there are still biological barriers and other obstacles limiting gene and drug delivery efficacy. Currently available strategies for gene therapy are not cost-effective, and they do not deliver the genetic cargo effectively to target sites. With rapid advancements in nanotechnology, novel gene delivery systems are introduced as nonviral vectors such as protein, peptide, and amino acid-based nanostructures. These nano-based delivery platforms can be tailored into functional transformation using proteins and peptides ligands based nanocarriers, usually overexpressed in the specified diseases. The purpose of this review is to shed light on traditional and nanotechnology-based methods to detect amino acids, peptides, and proteins. Furthermore, new insights into the potential of amino protein-based nanoassemblies for targeted drug delivery or gene transfer are presented.

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Glutathione Reductase-Sensitive Polymeric Micelles for Controlled Drug Delivery on Arthritic Diseases

Cited by 19 publications

References 52 publications

Cellular Uptake of Three Different Nanoparticles in an Inflammatory Arthritis Scenario versus Normal Conditions

Cellular Uptake of Three Different Nanoparticles in an Inflammatory Arthritis Scenario versus Normal Conditions

Weak Polyelectrolytes as Nanoarchitectonic Design Tools for Functional Materials: A Review of Recent Achievements

Amino Acids, Peptides, and Proteins: Implications for Nanotechnological Applications in Biosensing and Drug/Gene Delivery

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