Cited by 262Nanoparticle-Based Drug DeliveryTuberculosis Research and EpidemiologyMesoporous Materials and Catalysis

The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.

Targeted Intracellular Delivery of Antituberculosis Drugs to Mycobacterium tuberculosis-Infected Macrophages via Functionalized Mesoporous Silica Nanoparticles

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Abstract

Delivery of antituberculosis drugs by nanoparticles offers potential advantages over free drug, including the potential to target specifically the tissues and cells that are infected by Mycobacterium tuberculosis , thereby simultaneously increasing therapeutic efficacy and decreasing systemic toxicity, and the capacity for prolonged release of drug, thereby allowing less-frequent dosing. We have employed mesoporous silica nanoparticle (MSNP) drug delivery systems either equipped with a polyethyleneimine (PEI) coating to release rifampin or equipped with cyclodextrin-based pH-operated valves that open only at acidic pH to release isoniazid (INH) into M. tuberculosis -infected macrophages. The MSNP are internalized efficiently by human macrophages, traffic to acidified endosomes, and release high concentrations of antituberculosis drugs intracellularly. PEI-coated MSNP show much greater loading of rifampin than uncoated MSNP and much greater efficacy against M. tuberculosis- infected macrophages. MSNP were devoid of cytotoxicity at the particle doses employed for drug delivery. Similarly, we have demonstrated that the isoniazid delivered by MSNP equipped with pH-operated nanovalves kill M. tuberculosis within macrophages significantly more effectively than an equivalent amount of free drug. These data demonstrate that MSNP provide a versatile platform that can be functionalized to optimize the loading and intracellular release of specific drugs for the treatment of tuberculosis.

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Crossref · 10.1128/aac.06049-11

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Research works printed but not linked: 1

  1. MalabarbaA FerrariP DepaoliA GalloGG CavalleriB. 1986. Synthesis and conformation of some acetyl derivatives of rifampicin. Farmaco Sci. 41:131–150.

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Metadata

Authors
Clemens, D. L., Lee, B.-Y., Xue, M., Thomas, C. R., Meng, H., Ferris, D., Nel, A. E., Zink, J. I., & Horwitz, M. A.
Affiliations
  • University of California, Los Angeles (US)
  • Division of NanoMedicine, Department of Medicine, University of California, Los Angeles, California, USA
  • California NanoSystems Institute (US)
Venue
Antimicrobial Agents and Chemotherapy
Published
2012-05
Volume
56
Issue
5
Pages
2535-2545
ISSN
  • 0066-4804 (ISSN-L)
  • 1098-6596
OpenAlex
W2021068830
Cited by
260
References
49
Citations by year
2026: 12 · 2025: 8 · 2024: 17 · 2023: 24 · 2022: 24 · 2021: 29 · 2020: 24 · 2019: 22 · 2018: 14 · 2017: 16 · 2016: 15 · 2015: 21 · 2014: 21 · 2013: 8 · 2012: 2
FWCI
6.74
Type
journal article
Language
en
Open access
Locations
  • Antimicrobial Agents and Chemotherapy (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders
  • Foundation for the National Institutes of Health
  • Bill and Melinda Gates Foundation
  • National Cancer Institute (R01CA133697, CA 133697)
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
  • Physical Sciences › Materials Science › Materials Chemistry › Mesoporous Materials and Catalysis
Keywords
mesoporous silica nanoparticles, Mycobacterium tuberculosis, infected macrophages, rifampicin, isoniazid, polyethyleneimine coating, intracellular drug release, endosomal acidification, tuberculosis treatment
MeSH terms
Antitubercular Agents, Cell Line, Cell Survival, Cyclodextrins, Drug Compounding, Humans, Hydrogen-Ion Concentration, Isoniazid, Macrophages, Mycobacterium tuberculosis, Phagocytosis, Polyethyleneimine, Rifampin, Silicon Dioxide, Colony Count, Microbial, Porosity, Drug Delivery Systems, Microscopy, Electron, Transmission, Microbial Viability, Nanoparticles

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