Kidney-targeted drug delivery via rhein-loaded polyethyleneglycol-&lt;em&gt;co&lt;/em&gt;-polycaprolactone-&lt;em&gt;co&lt;/em&gt;-polyethyleneimine nanoparticles for diabetic nephropathy therapy

Chen, Danfei; Han, Shunping; Zhu, Yongqin; Hu, Fang; Wei, Yinghui; Wang, Guowei

doi:10.2147/ijn.s166445

Cited by 53 publications

(29 citation statements)

References 67 publications

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“…Specifically, nanoparticles pass through the glomerular filtration membrane if they are smaller than 10 nm, whereas those with sizes larger than 100 nm seldom distribute into kidney because they are mostly trapped by liver and spleen 12-14. In sharp contrast, nanoparticles with sizes of 30 ~ 80 nm can be sequestered by the mesangium of kidney in DN, thereby achieving reduced liver retention and hepatotoxicity 14-16. In our previous work, nanoparticles with a size of 75.4 ± 2.9 nm exhibited specific kidney distribution in DN model mice 16.…”

Section: Introductionmentioning

confidence: 99%

“…In sharp contrast, nanoparticles with sizes of 30 ~ 80 nm can be sequestered by the mesangium of kidney in DN, thereby achieving reduced liver retention and hepatotoxicity 14-16. In our previous work, nanoparticles with a size of 75.4 ± 2.9 nm exhibited specific kidney distribution in DN model mice 16. To date, several reports have demonstrated RH-loaded nanoparticle delivery system for improving solubility and blood circulation time 17, 18, but an efficient nanoparticle targeted delivery for DN therapy remains under investigation.…”

Section: Introductionmentioning

confidence: 99%

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Kidney-targeted rhein-loaded liponanoparticles for diabetic nephropathy therapy via size control and enhancement of renal cellular uptake

Wang

Chen

et al. 2019

Theranostics

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The optimization of nanoparticle size for passing through glomerular filtration membrane, inefficient renal cellular uptake and rapid urinary excretion of nanoparticles are the major obstacles for renal disease treatment via a nanoparticle delivery system. Herein, we propose a concept of a two-step nanoparticular cascade of size control and enhancement of renal cellular uptake to overcome the renal delivery obstacles.Methods: We prepared kidney-targeted rhein (RH)-loaded liponanoparticles (KLPPR) with a yolk-shell structure composed by polycaprolactone-polyethyleneimine (PCL-PEI)-based cores and kidney targeting peptide (KTP)-modified lipid layers. The KLPPR size within the range of 30 ~ 80 nm allowed KLPPR distribute into kidney by passing through the glomerular filtration membrane and the KTP (sequence: CSAVPLC) decoration promoted the renal cellular uptake and endocytosis via a non-lysosomal pathway.Results: The KLPPR had an average size of 59.5±6.2 nm and exhibited high RH loading, sustained release, good stability and biocompatibility, rapid cellular uptake in HK-2 cells. In addition, intravenous administration of KLPPR resulted in excellent kidney-targeted distribution and low urinary excretion in mice with streptozocin-induced diabetic nephropathy (DN), lowered the parameters of urea nitrogen, serum creatinine and kidney index, as well as facilitated the recovery of renal physiological function in improving the levels of urinary creatinine and the creatinine clearance rate by suppressing secretion and accumulation of fibronectin and TGF-β1.Conclusion: Definitely, KLPPR were able to target the diseased kidney and improve the therapeutic effect of RH on DN by exploiting the two-step nanoparticular cascade of size control and enhancement of cellular uptake. This study offers a promising strategy for renal diseases treatment using liponanoparticle delivery system.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Kidney-targeted rhein-loaded liponanoparticles for diabetic nephropathy therapy via size control and enhancement of renal cellular uptake

Wang

Chen

et al. 2019

Theranostics

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“…A clinical trial indicated that patients with DN were treated by rhein supplementation got better through decreasing Scr, serum cystatin C (CysC), and UAER (Xiao et al, 2011). In addition, the use of rhein capsules has already been approved in Phase II clinical trials (clinical trial approval number: 2008L03643) (Chen et al, 2018). In summary, the clinical trials and animal experiments of rhein need mutual feedback and coordinated development, so that rhein can be applied to the clinical treatment of DN at an early stage.…”

Section: Implication For Further Studiesmentioning

confidence: 99%

A Significant Association Between Rhein and Diabetic Nephropathy in Animals: A Systematic Review and Meta-Analysis

Zheng

Yin

et al. 2019

Front. Pharmacol.

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Background: Rhein is considered to have beneficial influence on diabetic nephropathy. Animal experiments suggested that the mechanisms of rhein against diabetic nephropathy may involve many processes, but the credibility of the evidence is unclear. Therefore, we conducted systematic review and meta-analysis of pre-clinical animal data to assess the current evidence for rhein effects and mechanisms in treating diabetic nephropathy.Methods: The databases of PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, VIP information database, Wanfang Data Information Site, and Chinese Biomedical Literature were searched for this review. SYRCLE's risk of bias tool for animal studies was applied to assess the methodological quality of studies. A metaanalysis was performed according to the Cochrane Handbook for Systematic Reviews of Interventions by using RevMan 5.3 and STATA/SE 12.0 software. This study was registered with PROSPERO, number CRD42018105220.Results: Twenty-five studies involving 537 animals were included. There was significant association of rhein with levels of blood glucose (P < 0.05), serum creatinine (Scr) (P < 0.05), urine protein (P < 0.05), kidney tubules injury index (P < 0.05), relative area of kidney collagen (P < 0.05), transforming growth factor-β 1 (P < 0.05), malondialdehyde (P < 0.05), and superoxide dismutase (P < 0.05) compared with that in the control group. No significant association between rhein and endothelin (P > 0.05) was found. Subgroup analysis showed that the hypoglycemic effect of rhein on type 2 diabetic nephropathy was better than on type 1 diabetic nephropathy (P < 0.05).Conclusions: These findings suggested that rhein has beneficial effects on animal models of diabetic nephropathy, and that the mechanisms are mostly involved with ameliorating levels of TGF-β 1 , renal fibrosis, metabolism, and oxidative stress status. However, some factors such as possible publication bias, methodological quality, and sample size may affect the accuracy of positive findings. These limitations suggested Frontiers in Pharmacology | www.frontiersin.org Rhein for Diabetic Nephropathy Hu et al.that a cautious interpretation of the positive results of this systematic review and metaanalysis is necessary. Therefore, high methodological quality and well-reported animal experiments are needed in future research.

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“…of DN [4]. Despite the exact pathogenesis of DN is still not clear, a large number of causes are considered to be related to the development of DN, including inflammatory response and oxidative response [5,6].…”

Section: Introductionmentioning

confidence: 99%

“…DN is the primary root of morbidity and mortality in diabetic patients. Unfortunately, still nowadays, no effective therapeutic strategies are available to ameliorate and reverse the progression of DN [4]. Despite the exact pathogenesis of DN is still not clear, a large number of causes are considered to be related to the development of DN, including inflammatory response and oxidative response [5,6].…”

Section: Introductionmentioning

confidence: 99%

Luteolin Attenuates Diabetic Nephropathy through Suppressing Inflammatory Response and Oxidative Stress by Inhibiting STAT3 Pathway

Zhang

Liu

et al. 2020

Exp Clin Endocrinol Diabetes

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Background Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD). DN has many pathological changes, but tubular injury is considered to be a crucial pathological feature and plays a key role in the progression of DN. Accumulating studies have confirmed that Luteolin (3,4,5,7-tetrahydroxyflavone, Lut) possesses anti-inflammatory and antioxidant activities, which may play a role in kidney protection in DN. Objectives This paper described the effects of Lut on appropriated tubular injury in the kidneys of db/db mice and searched the possible mechanisms underlying the kidney protection effect in DN. Methods Twelve-week-old male C57BL/6 J db/db and C57BL/6 J db/m mice were used for the animal experiments. They were organized into the following five groups for the animal experiments: a db/m group (control, n=6); a db/db group(n=8) ; a db/db group receiving Lut (10 mg/kg/day, n=8)treatment by oral gavage; a db/db group receiving stattic (a selective STAT3 inhibitor,50 mg/Kg/day, n=8) treatment by oral gavage and a db/db group receiving both stattic and Lut treatment by oral gavage. Results In this study, we found that Lut might ameliorate glomerular sclerosis and interstitial fibrosis in DN mouse models through inhibiting the inflammatory response and oxidative stress. And it might play its biological function mainly through repressing the STAT3 activation. Conclusions Lut attenuates DN mainly via suppression of inflammatory response and oxidative response. STAT3 pathway is the potential target, which ultimately reduces renal fibrosis and delays the progress of DN.

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Kidney-targeted drug delivery via rhein-loaded polyethyleneglycol-<em>co</em>-polycaprolactone-<em>co</em>-polyethyleneimine nanoparticles for diabetic nephropathy therapy

Cited by 53 publications

References 67 publications

Kidney-targeted rhein-loaded liponanoparticles for diabetic nephropathy therapy via size control and enhancement of renal cellular uptake

Kidney-targeted rhein-loaded liponanoparticles for diabetic nephropathy therapy via size control and enhancement of renal cellular uptake

A Significant Association Between Rhein and Diabetic Nephropathy in Animals: A Systematic Review and Meta-Analysis

Luteolin Attenuates Diabetic Nephropathy through Suppressing Inflammatory Response and Oxidative Stress by Inhibiting STAT3 Pathway

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