Platinum pharmacokinetics in mice following inhalation of cisplatin dry powders with different release and lung retention properties

作     者：Levet, Vincent Merlos, Romain Rosiere, Remi Amighi, Karim Wauthoz, Nathalie 

作者机构：Univ Libre Bruxelles Lab Pharmaceut & Biopharmaceut Fac Pharm Bd Triomphe CP 207Campus Plaine B-1050 Brussels Belgium 

出 版 物：《INTERNATIONAL JOURNAL OF PHARMACEUTICS》 (国际制药学杂志)

年 卷 期：2017年第517卷第1-2期

页      面：359-372页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 10[医学] 

主　　题：Dry powder for inhalation Lung retention Lung cancer chemotherapy Controlled release Stealth formulation Solid lipid microparticles Cisplatin 

摘      要：Pharmacokinetics of cisplatin administered by the pulmonary route were established in mice using dry powders inhaler (DPI) formulations showing immediate (F1) and controlled release (CR, solid lipid microparticles) in vitro, without (F2) or with PEGylated excipients (F3, F4). Formulation administration was realized using dry powder blends (correspondingly named thereafter F1(B) to F4(B)) able to reproducibly deliver particles in vivo using a DP-4M Dry Powder Insufflator (TM). Their platinum pharmacokinetics were established over 48 h in lungs, total blood and non-target organs vs. IV and endotracheal nebulization (EN). EN and FIB were rapidly distributed from the lungs (t(1/2)(i) 2.6 and 5.0 min). F2(B) was eliminated in similar to 1 h (t(1/2)(i) 9.0 min). F3(B) lung retention was sustained for similar to 7 h (t(1/2)(i) 59.9 min), increasing lung AUC 11-, 4 and 3-fold vs. IV, F1(B) and F2(B). Total blood t(max) were higher and AUC and C-max lower using the pulmonary route vs. IV. Kidney C-max was reduced 6-, 2- and 3-fold for F1(B), F2(B) and F3(B). AUC in kidneys were 2- to 3-fold lower for F1(B) and F2(B) vs. IV but comparable for IV vs. F3(B), probably because of kidney saturation. PEGylated solid lipid microparticles provided cisplatin particles with interesting lung retention and CR properties. (C) 2016 Elsevier B.V. All rights reserved.