Biodistribution and elimination pathways of PEGylated recombinant human deoxyribonuclease I after pulmonary delivery in mice

Conjugation of recombinant human deoxyribonuclease I (rhDNase) to polyethylene glycol (PEG) 20 40 kDa was previously shown prolong the residence time rhDNase in lungs mice after pulmonary delivery while preserving its full enzymatic activity. This work aimed study fate native and PEGylated elucidate their biodistribution elimination pathways intratracheal instillation mice. In vivo fluorescence imaging revealed that PEG30 kDa-conjugated (PEG30-rhDNase) retained mouse for a significantly longer period than (12 days vs 5 days). Confocal microscopy confirmed presence lung airspaces at least 7 days. contrast, unconjugated cleared from lumina within 24 h only found parenchyma alveolar macrophages thereafter. Systemic absorption intact PEG30-rhDNase observed. However, this lower latter. Catabolism, primarily secondarily systemically followed by renal excretion byproducts were predominant both rhDNase. Catabolism nevertheless more extensive protein. On other hand, mucociliary clearance appeared play less prominent role those proteins delivery. The prolonged appears ideal mucolytic action patients with cystic fibrosis.