Oral delivery of metformin by chitosan nanoparticles for polycystic kidney disease

Wang, Jonathan; Chin, Deborah; Poon, Christopher; Mancino, Valeria; Pham, Jessica; Li, Hui; Ho, Pei‐Yin; Hallows, Kenneth R.; Chung, Eun Ji

doi:10.1016/j.jconrel.2020.10.047

Cited by 58 publications

(39 citation statements)

References 105 publications

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“…Selective targeting of drugs such as metformin to the kidneys may afford much higher levels of drug delivery locally while preventing off-target effects or potential toxicities (e.g., lactic acidosis), which may be especially important in patients who have more advanced CKD with ADPKD (77). Of note, nanoparticle delivery platforms involving peptide amphiphile micelles that specifically target kidneys appear particularly promising in this regard for drug delivery in ADPKD and other kidney diseases (78,79). The relevant targets of metformin are not yet fully clear but, in addition to kidney epithelial cells, may also include extrarenal targets that have disease-modifying effects (36).…”

Section: Discussionmentioning

confidence: 99%

Metformin improves relevant disease parameters in an autosomal dominant polycystic kidney disease mouse model

Pastor-Soler

Pham

et al. 2022

American Journal of Physiology-Renal Physiology

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Autosomal dominant polycystic kidney disease (ADPKD), caused by mutations in the PKD1 or PKD2 genes encoding polycystins, presents with progressive development of kidney cysts and eventual end-stage kidney disease (ESKD) with limited treatment options. Previous work showed that metformin reduces cyst growth in rapid ADPKD mouse models via inhibition of CFTR-mediated fluid secretion, mTOR, and cAMP pathways. The present study importantly tested the effectiveness of metformin as a therapy for ADPKD in a more clinically relevant Pkd1RC/RC mouse model, homozygous for the R3277C knock-in point mutation in the Pkd1 gene. This mutation causes ADPKD in humans. Pkd1RC/RC male and female mice, which have slow progression to ESKD, received metformin (300 mg/kg/day in drinking water vs. water alone) from 3 to 9 or 12 months of age. As previously reported, Pkd1RC/RC females had a more severe disease phenotype than males. Metformin treatment reduced the ratio of total kidney weight to body weight relative to age- and sex-matched untreated controls at both 9 and 12 months and reduced cystic index in females at 9 months. Metformin also increased glomerular filtration rate (GFR), lowered systolic blood pressure, improved anemia, and lowered blood urea nitrogen levels relative to controls in both sexes. Moreover, metformin reduced gene expression of key inflammatory markers and both gene and protein expression of kidney injury marker-1 and cyclin-dependent kinase-1 vs. untreated controls. Altogether, these findings suggest several beneficial effects of metformin in this highly relevant slowly progressive ADPKD mouse model, which may help inform new ADPKD therapies in patients.

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Section: Discussionmentioning

confidence: 99%

Metformin improves relevant disease parameters in an autosomal dominant polycystic kidney disease mouse model

Pastor-Soler

Pham

et al. 2022

American Journal of Physiology-Renal Physiology

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“…Yuan and others found that LMWC uptake was considerably reduced in megalin-shedding animals, implying that the LMWC might be entered into the proximal tubular cells via the megalin receptor ( Yuan et al, 2009 ). Wang et al have investigated that chitosan nanoparticles (CS-NP) promising as drug delivery platforms for oral delivery in kidney disease ( Wang J et al, 2021 ).…”

Section: Kidney Targeted Nanoparticle Drug Delivery Systemmentioning

confidence: 99%

Role of Nanotechnology and Their Perspectives in the Treatment of Kidney Diseases

Merlin

2022

Front. Genet.

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Nanoparticles (NPs) are differing in particle size, charge, shape, and compatibility of targeting ligands, which are linked to improved pharmacologic characteristics, targetability, and bioavailability. Researchers are now tasked with developing a solution for enhanced renal treatment that is free of side effects and delivers the medicine to the active spot. A growing number of nano-based medication delivery devices are being used to treat renal disorders. Kidney disease management and treatment are currently causing a substantial global burden. Renal problems are multistep processes involving the accumulation of a wide range of molecular and genetic alterations that have been related to a variety of kidney diseases. Renal filtration is a key channel for drug elimination in the kidney, as well as a burgeoning topic of nanomedicine. Although the use of nanotechnology in the treatment of renal illnesses is still in its early phases, it offers a lot of potentials. In this review, we summarized the properties of the kidney and characteristics of drug delivery systems, which affect a drug’s ability should focus on the kidney and highlight the possibilities, problems, and opportunities.

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“…Wang et al. ( 2021 ) used chitosan to make the MET nanoparticles for polycystic kidney disease treatment and found a higher AUC, as well as controlled release, improving the delivery of the drug accumulated in some organs, mainly in the intestine. Wook Huh et al.…”

Section: Discussionmentioning

confidence: 99%

In vitro-in vivo availability of metformin hydrochloride-PLGA nanoparticles in diabetic rats in a periodontal disease experimental model

Pereira

Lima

Silva-Júnior

et al. 2021

Pharmaceutical Biology

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Oral delivery of metformin by chitosan nanoparticles for polycystic kidney disease

Cited by 58 publications

References 105 publications

Metformin improves relevant disease parameters in an autosomal dominant polycystic kidney disease mouse model

Metformin improves relevant disease parameters in an autosomal dominant polycystic kidney disease mouse model

Role of Nanotechnology and Their Perspectives in the Treatment of Kidney Diseases

In vitro-in vivo availability of metformin hydrochloride-PLGA nanoparticles in diabetic rats in a periodontal disease experimental model

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