Inhalable liposomal formulation for vasoactive intestinal peptide.
Inhalation of vasoactive intestinal peptide (VIP) was suggested as promising treatment option of various lung diseases like asthma and pulmonary hypertension. However, the medical use of peptides is limited by their short half-life due to rapid enzymatic degradation in the airways. For that reason, we recently developed unilamellar nano-sized VIP-loaded liposomes (VLL). Now we investigated their applicability for inhalation purposes. After nebulisation by a mouthpiece ventilation inhaler we found the particle size almost unaffected, being in a size range appropriate for bronchiolar deposition; we observed no peptide release due to nebulisation. The VIP release kinetics from VLL were tested by an ex vivo vasorelaxation model. Exposure to target organs revealed an immediate response, which was significantly retarded for VLL as compared to free VIP (p=0.001). Using vasorelaxation as endpoint, we observed a sustained release and an extended pharmacological effect compared to equimolar free VIP. The liposomes have the potential to improve VIP inhalation therapy by providing a "dispersible peptide depot" in the bronchi. Thereby, the release of VIP from liposomes may be triggered by exposure to cells, i.e. directly by ligand-receptor interactions.
Hajos
Franz
F
Medical University Vienna, Department of Internal Medicine-1, Division: Institute of Cancer Research, Borschkegasse 8a, A-1090 Vienna, Austria.
Stark
Brigitte
B
Hensler
Sigrid
S
Prassl
Ruth
R
Mosgoeller
Wilhelm
W
D000280:Administration, Inhalation; D000818:Animals; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004356:Drug Storage; D005765:Gastrointestinal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D014660:Vasoactive Intestinal Peptide / Q000008:administration & dosage* / Q000493:pharmacokinetics
D004337:Drug Carriers; D005765:Gastrointestinal Agents; D007202:Indicators and Reagents; D008081:Liposomes; D014660:Vasoactive Intestinal Peptide