Immunosuppressive Activity of Size-Controlled PEG-PLGA Nanoparticles Containing Encapsulated Cyclosporine A

Tang, Li; Azzi, Jamil; Kwon, Mincheol; Mounayar, Marwan; Tong, Rong; Yin, Qian; Moore, Richard O.; Skartsis, Nikolaos; Fan, Timothy M.; Abdi, Reza; Cheng, Jianjun

doi:10.1155/2012/896141

Cited by 43 publications

(37 citation statements)

References 33 publications

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“…Previous ex vivo studies 40,41 have demonstrated that encapsulation of CsA in PLGA nanoparticles results in a greater sustained immunosuppressive effect, which is contradictory to our results. This discrepancy seems to be due to the experimental design of the studies.…”

Section: Disclosurecontrasting

confidence: 99%

Liver-targeted cyclosporine A-encapsulated poly (lactic-co-glycolic) acid nanoparticles inhibit hepatitis C virus replication

Jyothi

Beloor

et al. 2015

IJN

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Therapeutic options for hepatitis C virus (HCV) infection have been limited by drug resistance and adverse side effects. Targeting the host factor cyclophilin A (CypA), which is essential for HCV replication, offers a promising strategy for antiviral therapy. However, due to its immunosuppressive activity and severe side effects, clinical application of cyclosporine A (CsA) has been limited as an antiviral agent. To overcome these drawbacks, we have successfully developed a liver-specific, sustained drug delivery system by conjugating the liver-targeting peptide (LTP) to PEGylated CsA-encapsulated poly (lactic-co-glycolic) acid (PLGA) nanoparticles. Furthermore, our delivery system exhibited high specificity to liver, thus contributing to the reduced immunosuppressive effect and toxicity profile of CsA. Finally, targeted nanoparticles were able to effectively inhibit viral replication in vitro and in an HCV mouse model. As a proof of principle, we herein show that our delivery system is able to negate the adverse effects of CsA and produce therapeutic effects in an HCV mouse model.

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Section: Disclosurecontrasting

confidence: 99%

Liver-targeted cyclosporine A-encapsulated poly (lactic-co-glycolic) acid nanoparticles inhibit hepatitis C virus replication

Jyothi

Beloor

et al. 2015

IJN

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“…Each block plays an important role, such as the presence of PEG helps to improve the stability of NPs by reducing NP aggregation (26). It also prevents phagocytosis by macrophages resulting in longer biological halflife (27).…”

Section: Resultsmentioning

confidence: 99%

Novel Pentablock Copolymer-Based Nanoparticulate Systems for Sustained Protein Delivery

et al. 2014

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Abstract. The design, synthesis, and application of novel biodegradable and biocompatible pentablock (PB) copolymers, i.e., polyglycolic acid-polycaprolactone-polyethylene glycol-polycaprolactonepolyglycolic acid (PGA-PCL-PEG-PCL-PGA) and polylactic acid-polycaprolactone-polyethylene glycolpolycaprolactone-polylactic acid (PLA-PCL-PEG-PCL-PLA) for sustained protein delivery, are reported. The PB copolymers can be engineered to generate sustained delivery of protein therapeutics to the posterior segment of the eye. PB copolymers with different block arrangements and molecular weights were synthesized by ring-opening polymerization and characterized by proton nuclear magnetic resonance ( 1 H-NMR), gel permeation chromatography (GPC), and X-ray diffraction (XRD) spectroscopy. Immunoglobulin G (IgG) was selected as a model protein due to its structural similarity to bevacizumab. The influence of polymer molecular weight, composition, and isomerism on formulation parameters such as entrapment efficiency, drug loading, and in vitro release profile was delineated. Crystallinity and molecular weight of copolymers exhibited a substantial effect on formulation parameters. A secondary structure of released IgG was confirmed by circular dichroism (CD) spectroscopy. In vitro cytotoxicity, cell viability, and biocompatibility studies performed on human retinal pigment epithelial cells (ARPE-19) and/or macrophage cell line (RAW 264.7) demonstrated PB copolymers to be excellent biomaterials. Novel PB polymers may be the answer to the unmet need of a sustained release protein formulation.

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“…Both free CsA and CsA-NPs displayed comparable suppression of T cell proliferation and production of inflammatory cytokines in various T cell assays in a dose-dependent manner. Our published and unpublished data in animals show the possibility of using polymeric nanoparticles as a promising drug delivery vehicle for treating diseases with improved efficacy and reduced toxicity (80,81).…”

Section: Future Prospectsmentioning

confidence: 91%

Calcineurin Inhibitors: 40 Years Later, Can’t Live Without …

Azzi

Sayegh

Mallat

2013

The Journal of Immunology

269

210

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Calcineurin inhibitors (CNIs) revolutionized the field of organ transplantation and remain the standard of care 40 years after the discovery of cyclosporine. The early impressive results of cyclosporine in kidney transplant recipients led to its subsequent use in other organ transplant recipients and for treatment of a variety of autoimmune diseases as well. In this review, we examine the discovery of CNIs, their mechanism of action, preclinical and clinical studies with CNIs, and the usage of CNIs in nontransplant recipients. We review the mechanisms of renal toxicity associated with CNIs and the recent efforts to avoid or reduce usage of these drugs. Although minimization strategies are possible, safe, and of potential long-term benefit, complete avoidance of CNIs has proven to be more challenging than initially thought.

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Immunosuppressive Activity of Size-Controlled PEG-PLGA Nanoparticles Containing Encapsulated Cyclosporine A

Cited by 43 publications

References 33 publications

Liver-targeted cyclosporine A-encapsulated poly (lactic-co-glycolic) acid nanoparticles inhibit hepatitis C virus replication

Liver-targeted cyclosporine A-encapsulated poly (lactic-co-glycolic) acid nanoparticles inhibit hepatitis C virus replication

Novel Pentablock Copolymer-Based Nanoparticulate Systems for Sustained Protein Delivery

Calcineurin Inhibitors: 40 Years Later, Can’t Live Without …

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