Liposomal nanoparticles encapsulating iloprost exhibit enhanced vasodilation in pulmonary arteries
Open Access
- 1 July 2014
- journal article
- Published by Taylor & Francis Ltd in International Journal of Nanomedicine
- Vol. 9, 3249-3261
- https://doi.org/10.2147/ijn.s63190
Abstract
Liposomal nanoparticles encapsulating iloprost exhibit enhanced vasodilation in pulmonary arteries Pritesh P Jain,1 Regina Leber,1,2 Chandran Nagaraj,1 Gerd Leitinger,3 Bernhard Lehofer,4 Horst Olschewski,1,5 Andrea Olschewski,1,6 Ruth Prassl,1,4 Leigh M Marsh11Ludwig Boltzmann Institute for Lung Vascular Research, 2Biophysics Division, Institute of Molecular Biosciences, University of Graz, 3Research Unit Electron Microscopic Techniques, Institute of Cell Biology, Histology, and Embryology, 4Institute of Biophysics, 5Division of Pulmonology, Department of Internal Medicine, 6Department of Anesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, Austria Prostacyclin analogues are standard therapeutic options for vasoconstrictive diseases, including pulmonary hypertension and Raynaud’s phenomenon. Although effective, these treatment strategies are expensive and have several side effects. To improve drug efficiency, we tested liposomal nanoparticles as carrier systems. In this study, we synthesized liposomal nanoparticles tailored for the prostacyclin analogue iloprost and evaluated their pharmacologic efficacy on mouse intrapulmonary arteries, using a wire myograph. The use of cationic lipids, stearylamine, or 1,2-di-(9Z-octadecenoyl)-3-trimethylammonium-propane (DOTAP) in liposomes promoted iloprost encapsulation to at least 50%. The addition of cholesterol modestly reduced iloprost encapsulation. The liposomal nanoparticle formulations were tested for toxicity and pharmacologic efficacy in vivo and ex vivo, respectively. The liposomes did not affect the viability of human pulmonary artery smooth muscle cells. Compared with an equivalent concentration of free iloprost, four out of the six polymer-coated liposomal formulations exhibited significantly enhanced vasodilation of mouse pulmonary arteries. Iloprost that was encapsulated in liposomes containing the polymer polyethylene glycol exhibited concentration-dependent relaxation of arteries. Strikingly, half the concentration of iloprost in liposomes elicited similar pharmacologic efficacy as nonencapsulated iloprost. Cationic liposomes can encapsulate iloprost with high efficacy and can serve as potential iloprost carriers to improve its therapeutic efficacy.Keywords: prostacyclin, cationic liposomes, pulmonary hypertension, wire myographKeywords
This publication has 38 references indexed in Scilit:
- Liposomal fasudil, a rho-kinase inhibitor, for prolonged pulmonary preferential vasodilation in pulmonary arterial hypertensionJournal of Controlled Release, 2013
- Cationic liposomes as carriers for aerosolized formulations of an anionic drug: Safety and efficacy studyEuropean Journal of Pharmaceutical Sciences, 2009
- Vincristine sulfate liposomes injection (Marqibo) in heavily pretreated patients with refractory aggressive non‐Hodgkin lymphomaCancer, 2009
- Liposomal Encapsulation of Deguelin: Evidence for Enhanced Antitumor Activity in Tobacco Carcinogen–Induced and Oncogenic K-ras–Induced Lung TumorigenesisCancer Prevention Research, 2009
- Association of vasoactive intestinal peptide with polymer-grafted liposomes: Structural aspects for pulmonary deliveryBiochimica et Biophysica Acta (BBA) - Biomembranes, 2007
- Single‐Dose Liposomal Amphotericin B in the Treatment of Visceral Leishmaniasis in India: A Multicenter StudyClinical Infectious Diseases, 2003
- Liposomal Drug FormulationsDrugs, 1998
- Sterically stabilized liposomesBiochimica et Biophysica Acta (BBA) - Reviews on Biomembranes, 1992
- Prolonged increase in digital blood flow following iloprost infusion in patients with systemic sclerosisHeart, 1987
- Diffusion of univalent ions across the lamellae of swollen phospholipidsJournal of Molecular Biology, 1965