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Engineering of VCAM-1-targeted nanostructured lipid carriers for delivery of melatonin against acute lung injury

Jian-Bo Jin1, Jing Li1, Hong-Bo Wang1

  • 1Department of Pharmacy, Ningbo University Affiliated Yangming Hospital, Yuyao, China.

International Journal of Biological Macromolecules
|March 15, 2024
PubMed
Summary

New nanostructured lipid carriers (NLCs) loaded with melatonin target lung inflammation in acute lung injury (ALI). This targeted delivery enhances therapeutic effects, offering a promising new treatment strategy for ALI patients.

Keywords:
Acute lung injuryMelatoninNanostructure lipid carrierPyroptosisVCAM-1

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Pharmacology

Background:

  • Acute lung injury (ALI) is a critical condition with limited effective treatments.
  • Current pharmacological interventions show insufficient efficacy in clinical settings.
  • Development of novel, efficient therapeutic strategies for ALI is urgently needed.

Purpose of the Study:

  • To develop targeted nanostructured lipid carriers (NLCs) for enhanced melatonin delivery to lung vascular endothelial cells.
  • To investigate the therapeutic potential of VCAM-1 antibody-conjugated melatonin-loaded NLCs (VCAM/MLT NLCs) for ALI treatment.

Main Methods:

  • Preparation and characterization of VCAM/MLT NLCs with specific size, drug loading, and release profiles.
  • Evaluation of targeted cellular delivery, internalization, and lung tissue accumulation mediated by VCAM-1 receptors.
  • Assessment of anti-inflammatory effects via NLRP3 inflammasome and pyroptosis pathways, including Sirtuin 1 modulation.

Main Results:

  • VCAM/MLT NLCs exhibited optimal physicochemical properties and sustained drug release.
  • Targeted conjugation enhanced cellular uptake and lung accumulation of melatonin.
  • Treatment with VCAM/MLT NLCs significantly reduced pulmonary inflammation by modulating NLRP3 inflammasome-dependent pyroptosis.

Conclusions:

  • VCAM/MLT NLCs represent a promising targeted drug delivery system for ALI.
  • This nanotechnology-based approach demonstrates significant therapeutic efficacy in both in vitro and in vivo models of ALI.
  • VCAM/MLT NLCs offer an efficient and novel treatment strategy for acute lung injury.