Tear lipocalin: potential for selective delivery of rifampin

• Published in: Biochimica et biophysica acta 2004-03, Vol.1688 (2), p.102-111
• Main Authors: Gasymov, Oktay K, Abduragimov, Adil R, Gasimov, Elshad O, Yusifov, Taleh N, Dooley, Alek N, Glasgow, Ben J
• Format: Article
• Language: English
• Subjects: Carrier Proteins - metabolism; Chromatography, Gel; Circular Dichroism; Drug Carriers - metabolism; Drug delivery; Humans; Hydrogen-Ion Concentration; Lipocalin 1; Mass Spectrometry; Molecular Structure; Oxidation-Reduction; Palmitic Acid - pharmacology; Protein Binding; Rifampin; Rifampin - chemistry; Rifampin - metabolism; Serum Albumin - chemistry; Serum Albumin - pharmacology; Spectrophotometry, Ultraviolet; Structure-Activity Relationship; Tear lipocalin; Tears - chemistry; Tears - metabolism; Tuberculosis; von Ebner's gland protein
• ISSN: 0925-4439; 0006-3002; 1879-260X
• DOI: 10.1016/j.bbadis.2003.11.006

The potential of ligand binding proteins as drug carriers and delivery systems has recently sparked great interest. We investigated the potential of tear lipocalin (TL) to bind the antibiotic, rifampin, and the environmental conditions for controlled release. To determine if TL binds rifampin, gel filtration was used to isolate protein fractions of tears. Rifampin was detected by absorbance spectroscopy in the elution fractions containing TL. The bound complex of rifampin–TL generates optical activity at about 360 nm, indicating a unique conformation at the binding site. Rifampin has a higher affinity for TL ( K d=128 μM) than albumin. Rifampin is released from the TL calyx in acidic conditions and is displaced by palmitic acid. Autooxidation of free rifampin begins in minutes but is delayed by at least 3 h in the presence of TL. These properties are conducive to stabilization and delivery of rifampin to tubercles that are acidic and rich in fatty acids. These studies show the potential of TL as a carrier for rifampin with controlled release to a targeted environment.