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A Semi-Automated and Reproducible Biological-Based Method to Quantify Calcium Deposition In Vitro
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Effect of kidney disease and vascular calcification on the circulation and distribution of

Vanessa Dos Passos Maio1,2, Roth-Visal Ung2, Karine Greffard2

  • 1Faculty of Pharmacy, Université Laval, 1050 ave de la Médecine, Quebec City, G1V 0A6, Canada. nicolas.bertrand@pha.ulaval.ca.

Nanoscale
|June 25, 2025
PubMed

Insights

New nanoparticles target vascular calcification (VC) in chronic kidney disease (CKD) models. Studies show safe distribution and potential for vitamin K delivery, advancing nanomedicine for VC treatment.

Area of Science:

  • Biomedical Engineering
  • Nanomedicine
  • Pharmacology

Background:

  • Cardiovascular disease (CVD) is a primary cause of mortality in chronic kidney disease (CKD) patients.
  • Vascular calcification (VC), a pathological hydroxyapatite deposition, exacerbates CVD in CKD but lacks effective treatments.
  • Tetracycline's affinity for hydroxyapatite suggests its potential for targeting VC.

Purpose of the Study:

  • To develop and evaluate poly(ethylene glycol)-b-poly(lactic acid) (PEG-PLA) nanoparticles functionalized with tetracycline for targeting VC.
  • To investigate the pharmacokinetics and biodistribution of these nanoparticles in CKD rat models.
  • To explore the impact of encapsulating vitamin K on nanoparticle pharmacokinetics and potential VC inhibition.

Main Methods:

  • Synthesis of PEG-PLA nanoparticles functionalized with tetracycline.
  • Administration of nanoparticles to healthy rats, CKD rats, and CKD rats with VC.
  • Analysis of nanoparticle circulation, biodistribution, and PEG elimination.
  • Assessment of nanoparticle distribution in calcified vascular walls.
  • Pharmacokinetic studies of vitamin K-loaded nanoparticles.

Main Results:

  • Nanoparticles exhibited similar blood and tissue exposures across all rat groups.
  • No significant accumulation of nanoparticles or PEG was observed in the body.
  • Encapsulating vitamin K altered drug pharmacokinetics, potentially enhancing systemic exposure.
  • Nanoparticles were localized within the calcified vascular wall.

Conclusions:

  • PEG-PLA nanoparticles functionalized with tetracycline show promise for targeting VC in CKD.
  • The developed nanomedicine approach demonstrates safe biodistribution and potential for drug delivery.
  • Further research is needed to optimize tetracycline-based targeting and nanomedicine for VC treatment.

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