title: Potential of the isolated lung technique for the examination of sildenafil absorption from lung-delivered poly(lactide-co-glycolide) microparticles.
abstract: Herein, we challenged the isolated lung (IL) technique to discriminate the performance of lung-delivered polymeric microparticles (MPs) having distinct drug release rates. For this purpose, sildenafil-loaded poly(lactide-co-glycolide) MPs were administered to the airspace of an IL model and the drug absorption profile was monitored. MPs (particle size of ~5μm) composed of PLGA of lower molecular weight (and glass transition temperature) manifested in the most rapid in vitro drug release (half-times ranging from <15 to ~200min). Moreover, microencapsulation resulted in a delayed sildenafil transfer over the air/perfusate barrier (half-times ranging from <5 to ~230min), where the actual ex vivo absorption profile depended on the release behavior of the utilized formulation. Finally, the obtained in vitro and ex vivo results were tested for level C, B and A correlations. The plotted data showed good agreement (R(2)>0.96) and the slopes of the resulting lines of regression (i.e., 0.80-0.85) indicated a slightly elevated in vitro drug release behavior. Overall, the IL model was able to differentiate between distinct microparticulate formulations and is, therefore, a valuable technique for early testing of potential inhalable controlled release medications.
authors: Medical Clinic II, Department of Internal Medicine, Justus-Liebig-Universität, Giessen, Germany; Department of Pharmaceutics and Biopharmacy, Philipps-Universität, Marburg, Germany. Electronic address: moritz.beck-broichsitter@innere.med.uni-giessen.de.
authors: Moritz
authors: M
authors: Beck-Broichsitter
authors: Medical Clinic II, Department of Internal Medicine, Justus-Liebig-Universität, Giessen, Germany.
authors: Katharina
authors: K
authors: Stoisiek
authors: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors: Adam
authors: A
authors: Bohr
authors: Unit of Functional and Adaptive Biology, UMR CNRS 8251, Université Paris Diderot, Paris, France.
authors: Leticia
authors: L
authors: Aragão-Santiago
authors: Medical Clinic II, Department of Internal Medicine, Justus-Liebig-Universität, Giessen, Germany.
authors: Tobias
authors: T
authors: Gessler
authors: Medical Clinic II, Department of Internal Medicine, Justus-Liebig-Universität, Giessen, Germany.
authors: Werner
authors: W
authors: Seeger
authors: Department of Pharmaceutics and Biopharmacy, Philipps-Universität, Marburg, Germany.
authors: Thomas
authors: T
authors: Kissel
mesh_terms: D000818:Animals; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding; D065546:Drug Liberation; D008168:Lung / Q000378:metabolism*; D010316:Particle Size; D011098:Polyglactin 910 / Q000737:chemistry*; D011817:Rabbits; D000068677:Sildenafil Citrate / Q000008:administration & dosage* / Q000493:pharmacokinetics; D044366:Transition Temperature; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D014665:Vasodilator Agents; D011098:Polyglactin 910; D000068677:Sildenafil Citrate
keywords: Controlled drug delivery; Correlation; Drug absorption; Drug release; Isolated lung; Polymeric microparticles