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Drugs must traverse multiple biological barriers, such as multi-layered skin, single-layered intestinal epithelium, and the plasma membrane, to reach their target sites within the body. The plasma membrane, a highly structured composite of phospholipids, carbohydrates, and proteins, is the cell's protective boundary, facilitating selective substance exchange.
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Polymeric carriers enhance targeted drug delivery by increasing efficacy while minimizing off-target effects. These carriers comprise a biodegradable polymeric backbone integrated with functional elements that enable targeting, improve physicochemical properties, and regulate drug release.Targeting MechanismsThe targeting ability of polymeric carriers is mediated by a homing device, which is a molecular recognition component designed to selectively bind to specific tissues or cells. Monoclonal...

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Related Experiment Video

Updated: Jun 28, 2026

Solid Lipid Nanoparticles SLNs for Intracellular Targeting Applications
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Advancing Cellular-Specific Delivery: Machine Learning Insights into Lipid Nanoparticles Design and Cellular Tropism.

Belal I Hanafy1, Michael J Munson2, Ramesh Soundararajan1

  • 1Advanced Drug Delivery, Pharmaceutical Sciences, Biopharmaceuticals R&D, AstraZeneca, Cambridge, CB2 0AA, United Kingdom.

Advanced Healthcare Materials
|May 6, 2025
PubMed
Summary

This study developed a data-driven method to engineer lipid nanoparticles (LNPs) for immune cell targeting, overcoming liver-specific delivery limitations. Optimized LNPs show enhanced immune cell uptake and reduced liver accumulation, expanding LNP therapeutic applications.

Keywords:
cellular tropismdesign of experimentlipid nanoparticlesmRNA deliverymachine learningprotein expression

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Area of Science:

  • Biotechnology
  • Nanomedicine
  • Drug Delivery Systems

Background:

  • Lipid nanoparticles (LNPs) are advanced nucleic acid delivery systems, but their primary liver targeting limits broader therapeutic use.
  • Developing LNPs with specific immune cell tropism is crucial for expanding their applications in treating immune-related diseases.

Purpose of the Study:

  • To engineer lipid nanoparticles (LNPs) for preferential immune cell targeting using a data-driven approach.
  • To identify LNP formulations that enhance immune cell specificity and reduce hepatic uptake.
  • To demonstrate the potential of tailored LNP compositions for selective cellular tropism.

Main Methods:

  • A data-driven approach combining design of experiments (DoE), high-throughput screening (HTS), and machine learning (ML).
  • Generation and in vitro screening of 180 LNP formulations with varied lipid compositions.
  • In vivo validation of selected LNPs for immune cell targeting and biodistribution.

Main Results:

  • Identification of LNP formulations with improved immune cell selectivity profiles through ML analysis.
  • Demonstration of preferential spleen expression in vivo for selected LNPs.
  • Successful redirection of LNP tropism away from hepatic cells towards immune cells.

Conclusions:

  • Tailoring LNP composition is essential for achieving selective cellular tropism.
  • The implemented data-driven workflow effectively identifies LNPs with desired immune cell targeting capabilities.
  • This strategy broadens the therapeutic potential of LNPs beyond liver-targeted applications.