Microencapsulated drug delivery: a new approach to pro-inflammatory cytokine inhibition

Abstract

Context: This article reviews the use of albumin microcapsules 3-4 µm in size containing cytokine inhibiting drugs which include neutralizing antibodies to TNF and IL1, CNI-1493, antisense oligonucleotides to TNF and NF-kappaB, and the antioxidant catalase.

Objective: Describe the effects, cellular uptake and distribution of microencapsulated drugs and the effect in both a peritonitis model of infection and a model of adjuvant-induced arthritis.

Methods: The studies performed by our group are reviewed, the only such studies available.

Results: Microencapsulation of these compounds produced high intracellular drug concentrations due to rapid uptake by phagocytic cells, including endothelial cells, without toxicity. All compounds produced excellent inhibition of TNF and IL1 resulting in improved animal survival in a peritonitis model of septic shock and inflammation in an arthritis model.

Conclusion: Albumin microencapsulated pro-inflammatory cytokine inhibiting compounds are superior to equivalent concentration of these compounds administered in solution form.

Figure 1

Scanning electron micrograph of albumin microspheres (magnification ×5500), size 1–7 μm.

Figure 2

Serial photographs of fluorescein-labelled albumin microspheres incubated with macrophages. Progressive phagocytosis of the microspheres is seen.

Figure 3

Endothelial cells were incubated with endotoxin. Fluorescein-labelled albumin microspheres were added and the percentage of cells containing microspheres was determined after 0.5, 1.0, 4.0 and 24 h. *p < 5 0.05 compared to the control group. Increased microsphere uptake by phagocytic cells was noted after endotoxin exposure.

Figure 4

Scanning electron micrograph of albumin microspheres (magnification ×5500), size 1–7 μm.

Figure 5

Development of arthritis and tissue swelling in rats after subcutaneous injection with M. butyricam.