Potential of the isolated lung technique for the examination of sildenafil absorption from lung-delivered poly(lactide-co-glycolide) microparticles

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• 作者：Moritz Beck-Broichsitter^a ; ^b ; ^{moritz.beck-broichsitter@innere.med.uni-giessen.de" class="auth_mail" title="E-mail the corresponding author} ; Katharina Stoisiek^a ; Adam Bohr^c ; Leticia Aragã ; o-Santiago^d ; Tobias Gessler^a ; Werner Seeger^a ; Thomas Kissel^b
• 关键词：ABC ; area between the curves ; BALF ; bronchoalveolar lavage fluid ; BSA ; bovine serum albumin ; dp ; median geometric microparticle diameter (based on the volume distribution) ; HPLC ; high pressure liquid chromatography ; IL ; isolated lung ; M ; amount of sildenafil released ; MDT ; mean dissolution time ; Mn ; number average molecular weight ; MRT ; mean residence time ; MPs ; microparticles ; n.a. ; not applicable ; n.d. ; not detected ; PLGA ; poly(lactide-co-glycolide) ; SD ; standard deviation ; SEM ; scanning elect
• 刊名：Journal of Controlled Release
• 出版年：2016
• 出版时间：28 March 2016
• 年：2016
• 卷：226
• 期：Complete
• 页码：15-20
• 全文大小：627 K

文摘

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 ~ 5 μm) 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 ~ 200 min). Moreover, microencapsulation resulted in a delayed sildenafil transfer over the air/perfusate barrier (half-times ranging from < 5 to ~ 230 min), 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 (R² > 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.