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Enhanced Macrophage Uptake of Spray-Dried Phosphatidylserine-Loaded Microparticles for Pulmonary Drug Delivery

Matthew T Freeman1, Arianne Parvaresh-Rizi2, Samantha A Meenach1,3

  • 1Department of Chemical Engineering, University of Rhode Island, Kingston, RI 02881 USA.

Journal of Drug Delivery Science and Technology
|January 20, 2025
PubMed

Insights

This study developed inhalable microparticles (MPs) for targeted drug delivery to alveolar macrophages. The MPs enhance drug uptake by macrophages, improving treatments for macrophage-associated diseases.

Area of Science:

  • Immunology
  • Nanotechnology
  • Drug Delivery

Background:

  • Macrophages are crucial for innate immunity but can harbor pathogens like SARS-CoV-2.
  • Current treatments for macrophage-associated diseases often require systemic delivery, leading to inefficiencies.
  • Targeted drug delivery to macrophages offers a promising therapeutic strategy.

Purpose of the Study:

  • To develop an inhalable dry powder microparticle (MP) formulation for targeted drug delivery to alveolar macrophages.
  • To achieve controlled release of therapeutics within macrophages.
  • To overcome limitations of conventional systemic drug delivery methods.

Main Methods:

  • Synthesized acetalated dextran (Ac-Dex) MPs using a one-step spray drying method.
  • Loaded MPs with curcumin (model therapeutic) and 1,2-dipalmitoyl-sn-glycero-3-phospho-L-serine (DPPS) to enhance macrophage uptake.
  • Evaluated MP uptake by RAW 264.7 macrophages and assessed pH-responsive drug release and aerosolization properties.

Main Results:

  • DPPS-loaded MPs showed significantly enhanced and macrophage-specific uptake compared to control MPs.
  • The microparticles demonstrated pH-responsive drug release.
  • In vitro aerosol dispersion analysis confirmed the potential for effective pulmonary delivery.

Conclusions:

  • The developed inhalable MPs demonstrate potential for targeted delivery and controlled release of therapeutics to alveolar macrophages.
  • DPPS-mediated uptake enhances therapeutic efficacy for macrophage-associated diseases.
  • This formulation offers a promising approach to improve treatment outcomes for pulmonary infections and inflammatory conditions.
Keywords:
Phosphatidylserineacetalated dextranmacrophagemicroparticlespulmonaryspray drying

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