Modeling nanoparticle delivery of TB drugs to granulomas

A. Grobler, Z. Perez Sierra, Hendrik J Viljoen

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Tuberculosis, which typically presents as a pulmonary disease, has a complex pathology. The primary site of infection, the Ghon focus, recruits immune cells and a granuloma forms. At earlier stages the granuloma is still vascularized, offering the best opportunity for drug treatment. In the more progressive state blood flow is reduced and a distinct caseous structure develops. Effective delivery of drugs to bacilli in the core of the granuloma becomes very difficult. It is perceivable that granuloma cores could create conditions where bacilli persist and develop resistance. In this study we analyze drug delivery to granulomas by means of a nanoparticle delivery system. The model consists of two parts; the overall distribution of the nanoparticles is described by a simple circulatory model and this result is used in the second part, focusing on transport in a capillary lined with macrophages. Nanoparticles enter the macrophages where they are metabolized and the drugs are released. The model reveals significant differences in drug concentrations between the plasma and macrophages. Based on the results of the model, strategies for improved drug delivery are proposed.

Original languageEnglish (US)
Pages (from-to)85-95
Number of pages11
JournalJournal of Theoretical Biology
Volume388
DOIs
StatePublished - Jan 7 2016

Fingerprint

granuloma
nanoparticles
Granuloma
Nanoparticles
Macrophage
Macrophages
Drugs
drugs
Drug Delivery
Bacilli
Drug delivery
Modeling
macrophages
Pharmaceutical Preparations
Drug therapy
Pulmonary diseases
Bacillus
Tuberculosis
Pathology
Blood Flow

Keywords

  • Bioavailability
  • Macrophages
  • Metabolizing rate
  • Pharmacodynamics

ASJC Scopus subject areas

  • Statistics and Probability
  • Modeling and Simulation
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

Cite this

Modeling nanoparticle delivery of TB drugs to granulomas. / Grobler, A.; Perez Sierra, Z.; Viljoen, Hendrik J.

In: Journal of Theoretical Biology, Vol. 388, 07.01.2016, p. 85-95.

Research output: Contribution to journalArticle

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