# Glycocalyx repair in sepsis using liposomal carriers of preassembled glycocalyx

> **NIH NIH R01** · NEW YORK MEDICAL COLLEGE · 2020 · $541,200

## Abstract

ABSTRACT
Endothelial glycocalyx (EG), a carbohydrate-rich outermost surface layer, is a guardian
of vascular functions. It is a sensor of the shear stress-activated endothelial nitric oxide
production and flow-induced vasodilation, harbinger of growth factors, extracellular
superoxide dismutase and anti-thrombin III, EG is a regulator of vascular permeability and
leukocyte trafficking across the vascular wall, and it protects receptors from
hyperstimulation by shielding them. EG is degraded in diverse cardiovascular, metabolic
and renal diseases, thus leading to impairment of all the above functions. One of these
conditions precipitating the loss of EG is septicemia, which is associated with high
morbidity and mortality. We observed that mice with the polymicrobial sepsis exhibit a
drastic reduction in the global volume of EG. Therefore, expeditious restoration of EG
represents a rational pathogenetic therapy. We have recently designed, synthesized and
tested in vitro, ex vivo and in vivo liposomal nanocarriers of preassembled glycocalyx.
This pharmacological intervention improved mechanotransduction and nitric oxide
synthesis, flow-induced vasodilation and renal microcirculation in endotoxemic mice. We
have presently designed and synthesized the second generation of liposomal
nanocarriers of preassembled glycocalyx featuring “stealth” liposomes with increased
half-life, gold-label, as well as an array of possible modifications and demonstrated that
they significantly improved survival of mice injected with the lethal dose of LPS. The
present proposal is aimed at exploration of validity and efficacy of this pharmacologic
approach in sepsis. We describe the steps to refine liposomal nanocarriers of
preassembled glycocalyx, monitoring of the fate of these gold-labeled liposomes – their
fusion with the plasma membrane, intracellular traffic, half-life in the vasculature.
Thereafter we shall determine the effect of intravenous injection of liposomal nanocarriers
on the course of sepsis and associated with it hemodynamic perturbations and the rate
of functional restoration of affected organs. Proposed studies should not only refine this
novel therapeutic tool but may also establish a pharmacologic approach to ameliorate
sepsis-induced multiorgan failure.

## Key facts

- **NIH application ID:** 9989137
- **Project number:** 5R01HL144528-02
- **Recipient organization:** NEW YORK MEDICAL COLLEGE
- **Principal Investigator:** MICHAEL S GOLIGORSKY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $541,200
- **Award type:** 5
- **Project period:** 2019-08-05 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989137

## Citation

> US National Institutes of Health, RePORTER application 9989137, Glycocalyx repair in sepsis using liposomal carriers of preassembled glycocalyx (5R01HL144528-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9989137. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*