The application of LbL-microcarriers for the treatment of chronic inflammation: monitoring the impact of LbL-microcarriers on cell viability

Macromol Biosci. 2015 Apr;15(4):546-57. doi: 10.1002/mabi.201400405. Epub 2015 Jan 7.

Abstract

Layer-by-Layer (LbL) coated microcarriers provide a multifunctional drug delivery system for therapeutic substances into specific cells. Inflammatory cells as polymorphonuclear leukocytes (PMNs) represent a particularly promising target for LbL-microcarriers transporting anti-inflammatory substances such as α1 -antitrypsin (AT). They facilitate a local, low-dose and time-controlled application of the assembled therapeutic to effectively inhibit destructive enzymes provided by PMNs. But besides therapeutic effects, microcarriers themselves are not expected to affect cell viability. Thus, the present study emphasizes the investigation of LbL-microcarriers regarding their necrotic or apoptotic influence on inflammatory cells. The detection of mitochondrial membrane potential changes, reporting the induction of cellular apoptosis, was completed by the detection of apoptotic changes of the nucleus and lactate dehydrogenase release reporting potential necrotic influences. Investigations of microcarrier interactions with HL-60 cells and blood-isolated PMNs show very low influence on necrosis and, in case of AT-functionalized microcarriers, even a prolonged maintenance of mitochondrial membrane potential underlining the high potential of LbL-microcarriers.

Keywords: Layer-by-Layer (LbL)- microcarrier; biopolymer; cell viability; drug delivery system; inflammatory cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Cell Survival / drug effects
  • Coated Materials, Biocompatible / administration & dosage
  • Coated Materials, Biocompatible / chemistry
  • Drug Delivery Systems*
  • HL-60 Cells
  • Humans
  • Inflammation / drug therapy*
  • Neutrophils / drug effects*
  • Neutrophils / pathology
  • alpha 1-Antitrypsin / administration & dosage*
  • alpha 1-Antitrypsin / chemistry

Substances

  • Coated Materials, Biocompatible
  • alpha 1-Antitrypsin