Hajos Franz, Stark Brigitte, Hensler Sigrid, Prassl Ruth, Mosgoeller Wilhelm
Medical University Vienna, Department of Internal Medicine-1, Division: Institute of Cancer Research, Borschkegasse 8a, A-1090 Vienna, Austria.
Int J Pharm. 2008 Jun 5;357(1-2):286-94. doi: 10.1016/j.ijpharm.2008.01.046. Epub 2008 Feb 3.
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.
吸入血管活性肠肽（VIP）被认为是治疗哮喘和肺动脉高压等多种肺部疾病的一种有前景的治疗选择。然而，由于肽类在气道中会迅速被酶降解，其半衰期较短，限制了它们在医学上的应用。因此，我们最近开发了单层纳米级载VIP脂质体（VLL）。现在我们研究了它们用于吸入的适用性。通过口件通气吸入器雾化后，我们发现颗粒大小几乎未受影响，处于适合细支气管沉积的尺寸范围内；我们未观察到因雾化导致的肽释放。通过体外血管舒张模型测试了VLL中VIP的释放动力学。暴露于靶器官显示出即时反应，与游离VIP相比，VLL的反应明显延迟（p = 0.001）。以血管舒张为终点，与等摩尔游离VIP相比，我们观察到持续释放和延长的药理作用。脂质体有可能通过在支气管中提供一个“可分散的肽库”来改善VIP吸入疗法。因此，脂质体中VIP的释放可能通过与细胞接触，即直接通过配体 - 受体相互作用来触发。
