Water soluble PEG-conjugate of xanthine oxidase inhibitor, PEG–AHPP micelles, as a novel therapeutic for ROS related inflammatory bowel diseases

Fang, Jun; Yin, Han; Лонг, Линг; Qin, Haibo; Ueda, Fumiko; Uemura, Kenichiro; Eguchi, Katsuhide; Bharate, Gahininath Y.; Maeda, Hiroshi

doi:10.1016/j.jconrel.2015.12.049

Cited by 23 publications

(12 citation statements)

References 47 publications

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“…Intravenous administration of nanocarriers such as liposomes, nano-micelles, and dendrimers are efficacious in inflammatory disease treatments [19][20][21]. Liposomes are widely used as they have low immunogenicity, and their surface properties can be easily modulated.…”

Section: Introductionmentioning

confidence: 99%

In Vivo Fluorescence Imaging of Passive Inflammation Site Accumulation of Liposomes via Intravenous Administration Focused on Their Surface Charge and PEG Modification

et al. 2021

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Nanocarriers such as liposomes have been attracting attention as novel therapeutic methods for inflammatory autoimmune diseases such as rheumatoid arthritis and ulcerative colitis. The physicochemical properties of intravenously administered nanomedicines enable them to target inflamed tissues passively. However, few studies have attempted to determine the influences of nanoparticle surface characteristics on inflammation site accumulation. Here, we aimed to study the effects of polyethylene glycol (PEG) modification and surface charge on liposome ability to accumulate in inflammatory sites and be uptake by macrophages. Four different liposome samples with different PEG modification and surface charge were prepared. Liposome accumulation in the inflammation sites of arthritis and ulcerative colitis model mice was evaluated by using in vivo imaging. There was greater PEG-modified than unmodified liposome accumulation at all inflammation sites. There was greater anionic than cationic liposome accumulation at all inflammation sites. The order in which inflammation site accumulation was confirmed was PEG-anionic > PEG-cationic > anionic > cationic. PEG-anionic liposomes had ~2.5× higher fluorescence intensity than PEG-cationic liposomes, and the PEG-liposomes had ~2× higher fluorescence intensity than non-PEG liposomes. All liposomes have not accumulated at the inflammation sites in healthy mice. Furthermore, cationic liposomes were taken up to ~10× greater extent by RAW264.7 murine macrophages. Thus, PEG-cationic liposomes that have the ability to accumulate in inflammatory sites via intravenous administration and to be taken up by macrophages could be useful.

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Section: Introductionmentioning

confidence: 99%

In Vivo Fluorescence Imaging of Passive Inflammation Site Accumulation of Liposomes via Intravenous Administration Focused on Their Surface Charge and PEG Modification

et al. 2021

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“…Furthermore, the capability of RhChr as a new ratiometric signal reporter to detect xanthine oxidase (XOD) activity in living organs was investigated. XOD is an important enzyme in the catabolism of purines, and its abnormal level is closely associated with many diseases such as gout, inflammation, and hypertension. , Evaluation of XOD activity is of great importance for the clinical diagnosis and the discovery of XOD inhibitor in drug development. Hypoxanthine (HX)-XOD is a classic system that is commonly used for the production of O 2 •– , which can be easily scavenged by HA .…”

Section: Resultsmentioning

confidence: 99%

“…XOD is an important enzyme in the catabolism of purines, and its abnormal level is closely associated with many diseases such as gout, inflammation, and hypertension. 41,42 Evaluation of XOD activity is of great importance for the clinical diagnosis and the discovery of XOD inhibitor in drug development. Hypoxanthine (HX)-XOD is a classic system that is commonly used for the production of O 2…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

Förster Resonance Energy Transfer-Based Fluorescent Probe for the Selective Imaging of Hydroxylamine in Living Cells

et al. 2019

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Hydroxylamine (HA) is an important product of cell metabolism and plays a significant role in many biological processes, and therefore, real-time imaging of HA is of great importance for the in-depth study of its physiological and pathological functions. However, a HA-specific fluorescent probe is currently lacking primarily because the highly selective HA-responsive site is undeveloped. To address this critical issue, we present a HA-specific FRET-based fluorescent probe (RhChr) for the selective detection of HA in living systems. Inspired by aza-Michael addition, the unsaturated system appended with an iminium ion was employed as the new HA-specific response site. In response to HA, RhChr provided a ratiometric signal output with excellent selectivity toward HA over biothiols and ammonia. We have demonstrated that RhChr could be applied for the ratiometric imaging of endogenous HA in living cells and the evaluation of xanthine oxidase (XOD) activity in living organs.

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“…The intravenous administration of nanoparticles, such as liposomes, nano-micelles, and dendrimers, is effective in treating inflammatory diseases. (105,106) Liposomes are widely used because of their low immunogenicity and the ease with which their surface properties can be tailored. The physicochemical properties of liposomes extend the advantage of passive targeting through the leaky vasculature of inflamed tissues.…”

Section: Controlling Physical Properties Of Liposomes To Provoke Accu...mentioning

confidence: 99%

In Vivo Topical and Systemic Distribution Kinetics of Liposomes with Various Properties for Application to Drug Delivery Systems

Ibaraki¹,

Kanazawa²

2022

Sensors and Materials

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Liposomes and lipid nanoparticles have been actively researched and developed as drug delivery carriers owing to their many advantages, such as high biocompatibility and degradability. Their in vivo kinetics depend on the route of administration, i.e., topical or intravenous, and their physical properties, such as particle size and surface charge. Designing liposomes that regulate in vivo kinetics and ensure efficient delivery to disease sites will result in excellent therapeutic effects. However, only a handful of studies have examined whether the characteristics and constituent lipids of liposomes can control histological and in vivo kinetics. In this review, we focus on the surface charge and polyethylene glycol (PEG) modifications of liposomes and evaluate their biodistribution. On the basis of our findings, we expound the effects of the intradermal permeability, inflammatory site accumulation, and physical properties of liposomes on systemic distribution kinetics.

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Water soluble PEG-conjugate of xanthine oxidase inhibitor, PEG–AHPP micelles, as a novel therapeutic for ROS related inflammatory bowel diseases

Cited by 23 publications

References 47 publications

In Vivo Fluorescence Imaging of Passive Inflammation Site Accumulation of Liposomes via Intravenous Administration Focused on Their Surface Charge and PEG Modification

In Vivo Fluorescence Imaging of Passive Inflammation Site Accumulation of Liposomes via Intravenous Administration Focused on Their Surface Charge and PEG Modification

Förster Resonance Energy Transfer-Based Fluorescent Probe for the Selective Imaging of Hydroxylamine in Living Cells

In Vivo Topical and Systemic Distribution Kinetics of Liposomes with Various Properties for Application to Drug Delivery Systems

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