Initial observations of cell-mediated drug delivery to the deep lung

Arun Kumar, Mark Glam, Nagwa El-Badri, Shyam Mohapatra, Edward Haller, Seungjoo Park, Leslie Patrick, Leigh Nattkemper, Dawn Vo, Don F. Cameron

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Using current methodologies, drug delivery to small airways, terminal bronchioles, and alveoli (deep lung) is inefficient, especially to the lower lungs. Urgent lung pathologies such as acute respiratory distress syn- drome (ARDS) and post-lung transplantation complications are difficult to treat, in part due to the method- ological limitations in targeting the deep lung with high efficiency drug distribution to the site of pathology. To overcome drug delivery limitations inhibiting the optimization of deep lung therapy, isolated rat Sertoli cells preloaded with chitosan nanoparticles were use to obtain a high-density distribution and concentration (92%) of the nanoparticles in the lungs of mice by way of the peripheral venous vasculature rather than the more commonly used pulmonary route. Additionally, Sertoli cells were preloaded with chitosan nanoparticles coupled with the anti-inflammatory compound curcumin and then injected intravenously into control or experimental mice with deep lung inflammation. By 24 h postinjection, most of the curcumin load (90%) delivered in the injected Sertoli cells was present and distributed throughout the lungs, including the perial- veloar sac area in the lower lungs. This was based on the high-density, positive quantification of both nanoparticles and curcumin in the lungs. There was a marked positive therapeutic effect achieved 24 h following curcumin treatment delivered by this Sertoli cell nanoparticle protocol (SNAP). Results identify a novel and efficient protocol for targeted delivery of drugs to the deep lung mediated by extratesticular Sertoli cells. Utilization of SNAP delivery may optimize drug therapy for conditions such as ARDS, status asthmat- icus, pulmonary hypertension, lung cancer, and complications following lung transplantation where the use of high concentrations of anti-inflammatory drugs is desirable, but often limited by risks of systemic drug toxicity.

Original languageEnglish (US)
Pages (from-to)609-618
Number of pages10
JournalCell transplantation
Volume20
Issue number5
DOIs
StatePublished - 2011
Externally publishedYes

Keywords

  • Deep lung
  • Drug delivery
  • Sertoli cells

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint

Dive into the research topics of 'Initial observations of cell-mediated drug delivery to the deep lung'. Together they form a unique fingerprint.

Cite this