In Vitro Efficacy of Polysaccharide-Based Nanoparticles Containing Disease-Modifying Antirheumatic Drugs

Zhang, Nan; Wardwell, Patricia R.; Bader, Rebecca A.

doi:10.1007/s11095-014-1329-z

Cited by 28 publications

(22 citation statements)

References 51 publications

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“…For sometime, polySia was believed to exert its effects exclusively through an anti-adhesive mechanism; however, more recently, its ability to impact signaling, either directly by controlling protein-protein interactions or indirectly by serving as a reservoir for signaling molecules, has been appreciated (Colley et al 2014;Schnaar et al 2014). Interestingly, polySia is also being used as a less immunogenic and more biodegradable substitute for polyethylene glycol (PEG) to enhance the stability and circulating half-life of therapeutic proteins [reviewed in Bader and Wardwell (2014), Colley et al (2014)], and as part of nanoparticles for drug delivery (Zhang et al 2014(Zhang et al , 2016. Please see below for a discussion of the protein specificity of polysialylation, its role cancer, and the article in this issue by Higuero and colleagues that discusses the role of glycans, including polySia, in CNS and PNS development and function (Higuero et al 2017).…”

Section: St8sia-ii and St8sia-ivmentioning

confidence: 99%

Sialylation of N-glycans: mechanism, cellular compartmentalization and function

Bhide

Colley

2016

Histochem Cell Biol

182

144

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Sialylated N-glycans play essential roles in the immune system, pathogen recognition and cancer. This review approaches the sialylation of N-glycans from three perspectives. The first section focuses on the sialyltransferases that add sialic acid to N-glycans. Included in the discussion is a description of these enzymes' glycan acceptors, conserved domain organization and sequences, molecular structure and catalytic mechanism. In addition, we discuss the protein interactions underlying the polysialylation of a select group of adhesion and signaling molecules. In the second section, the biosynthesis of sialic acid, CMP-sialic acid and sialylated N-glycans is discussed, with a special emphasis on the compartmentalization of these processes in the mammalian cell. The sequences and mechanisms maintaining the sialyltransferases and other glycosylation enzymes in the Golgi are also reviewed. In the final section, we have chosen to discuss processes in which sialylated glycans, both N- and O-linked, play a role. The first part of this section focuses on sialic acid-binding proteins including viral hemagglutinins, Siglecs and selectins. In the second half of this section, we comment on the role of sialylated N-glycans in cancer, including the roles of β1-integrin and Fas receptor N-glycan sialylation in cancer cell survival and drug resistance, and the role of these sialylated proteins and polysialic acid in cancer metastasis.

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Section: St8sia-ii and St8sia-ivmentioning

confidence: 99%

Sialylation of N-glycans: mechanism, cellular compartmentalization and function

Bhide

Colley

2016

Histochem Cell Biol

182

144

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“…In an in vitro model of RA, the polysialic acid-trimethyl chitosan NPs were used for delivery of dexamethasone and MTX. 80 These NPs were found to be equally effective as the free drugs. Theranostic polyethyleneimine (PEI)-superparamagnetic iron oxide NPs have also been used for the systemic delivery of IL-2/IL-15Rβ-siRNA to arthritic rats.…”

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confidence: 98%

Molecular targets in arthritis and recent trends in nanotherapy

Roy¹,

Kanwar²,

Kanwar³

2015

IJN

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Due to its severity and increasing epidemiology, arthritis needs no description. There are various forms of arthritis most of which are disabling, very painful, and common. In spite of breakthroughs in the field of drug discovery, there is no cure for arthritis that can eliminate the disease permanently and ease the pain. The present review focuses on some of the most successful drugs in arthritis therapy and their side effects. Potential new targets in arthritis therapy such as interleukin-1β, interleukin-17A, tumor necrosis factor alpha, osteopontin, and several others have been discussed here, which can lead to refinement of current therapeutic modalities. Mechanisms for different forms of arthritis have been discussed along with the molecules that act as potential biomarkers for arthritis. Due to the difficulty in monitoring the disease progression to detect the advanced manifestations of the diseases, drug-induced cytotoxicity, and problems with drug delivery; nanoparticle therapy has gained the attention of the researchers. The unique properties of nanoparticles make them highly attractive for the design of novel therapeutics or diagnostic agents for arthritis. The review also focuses on the recent trends in nanoformulation development used for arthritis therapy. This review is, therefore, important because it describes the relevance and need for more arthritis research, it brings forth a critical discussion of successful drugs in arthritis and analyses the key molecular targets. The review also identifies several knowledge gaps in the published research so far along with the proposal of new ideas and future directions in arthritis therapy.

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“…As anticipated based upon prior testing with the MH7A and SW-982 cell lines, 35,51 no changes in cellular proliferation were observed for IB3-1 cells with addition of PSA-TMC concentrations up to 10 mg/mL. 35 Therefore, bare nanoparticles administered at a concentration of 1 mg/mL for in vitro testing (1 mg/mL) were expected to yield a minimal change in cellular inflammatory response.…”

Section: Nanoparticle Preparation and Characterizationmentioning

confidence: 75%

“…Of note, the PSA-TMC nanoparticles did not exhibit cellular toxicity, as indicated by a cellular proliferation assay and consistent with data obtained from other cell types. 35,51 In contrast, Lipofectamine 2000 was associated with significant cellular toxicity, a highly undesirable characteristic when delivering anti-inflammatory therapeutics. The toxicity observed in this study is not limited to the IB3-1 cell type.…”

Section: Discussionmentioning

confidence: 99%

Immunomodulation of cystic fibrosis epithelial cells via NF‐κB decoy oligonucleotide‐coated polysaccharide nanoparticles

Wardwell

Bader

2014

J Biomedical Materials Res

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Activation of the transcription factor nuclear factor-kappa B (NF-κB) signaling pathway is associated with enhanced secretion of pro-inflammatory mediators and is thought to play a critical role in diseases hallmarked by inflammation, including cystic fibrosis (CF). Small nucleic acids that interfere with gene expression have been proposed as promising therapeutics for a number of diseases. However, applications have been limited by low cellular penetration and a lack of stability. Nano-sized carrier systems have been suggested as a means of improving the effectiveness of nucleic acid-based treatments. In this study, we successfully coated polysialic acid-N-trimethyl chitosan (PSA-TMC) nanoparticles with NF-κΒ decoy oligonucleotides (ODNs). To demonstrate anti-inflammatory activity, the decoy ODN-coated PSA-TMC nanoparticles were administered to an in vitro model of CF generated via interleukin-1β or P. aeruginosa lipopolysaccharides stimulation of IB3-1 bronchial epithelial cells. While free ODN and PSA-TMC nanoparticles coated with scrambled ODNs did not have substantial impacts on the inflammatory response, the decoy ODN-coated PSA-TMC nanoparticles were able to reduce the secretion of interleukin-6 and interleukin-8, pro-inflammatory mediators of CF, by the epithelial cells, particularly at longer time points. In general, the results suggest that NF-κB decoy ODN-coated TMC-PSA nanoparticles may serve as an effective method of altering the pro-inflammatory environment associated with CF.

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In Vitro Efficacy of Polysaccharide-Based Nanoparticles Containing Disease-Modifying Antirheumatic Drugs

Abstract: The present study verified that MTX and DM are able to retain bioactivity when loaded into PSA-TMC nanoparticles. Although in vitro efficacy was not increased, the in vivo efficacy will likely be enhanced by the site-specific targeting conferred by nanoparticle entrapment.

Cited by 28 publications

References 51 publications

Sialylation of N-glycans: mechanism, cellular compartmentalization and function

Sialylation of N-glycans: mechanism, cellular compartmentalization and function

Molecular targets in arthritis and recent trends in nanotherapy

Immunomodulation of cystic fibrosis epithelial cells via NF‐κB decoy oligonucleotide‐coated polysaccharide nanoparticles

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In Vitro Efficacy of Polysaccharide-Based Nanoparticles Containing Disease-Modifying Antirheumatic Drugs

Abstract: The present study verified that MTX and DM are able to retain bioactivity when loaded into PSA-TMC nanoparticles. Although in vitro efficacy was not increased, the in vivo efficacy will likely be enhanced by the site-specific targeting conferred by nanoparticle entrapment.

Cited by 28 publications

References 51 publications

Sialylation of N-glycans: mechanism, cellular compartmentalization and function

Sialylation of N-glycans: mechanism, cellular compartmentalization and function

Molecular targets in arthritis and recent trends in&nbsp;nanotherapy

Immunomodulation of cystic fibrosis epithelial cells via NF‐κB decoy oligonucleotide‐coated polysaccharide nanoparticles

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Product

Resources

About

Molecular targets in arthritis and recent trends in nanotherapy