期刊
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
卷 41, 期 2, 页码 244-253出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejps.2010.06.007
关键词
Nanoparticles; Solvent displacement; ouzo effect; Biodegradable polyesters; Salbutamol; Pulmonary drug delivery
资金
- German Ministry of Education and Research (BMBF) [13N8888]
As biodegradable nanoparticles meet with increasing interest for drug delivery applications, a series of investigations were carried out to understand the mechanism of the formation of drug-loaded nanoparticles using the solvent displacement method. Although previous explanations referred to Marangoni convection as the driving force for nanoprecipitation, recent publications describing the so-called ouzo effect sparked these current studies using a novel negatively charged polymer, poly(vinyl sulfonate-co-vinyl alcohol)-graft-poly(D,L-lactide-co-glycolide)(P(VS-VA)-g-PLGA), and a positively charged model drug, salbutamol. Interfacial tension did not influence the nanoparticle formation as would be expected if governed by Marangoni convection, but ternary phase diagrams outlined the so-called ouzo regions defining the polymer and solvent concentrations leading to stable nanoparticle suspensions for both this novel polymer and unmodified poly(D,L-lactide-co-glycolide) (PLGA). Physicochemical properties, morphology and drug loading of the nanoparticles were analyzed, and stable P(VS-VA)-g-PLGA nanoparticles with and without salbutamol ranged in size from 59-191 nm. The ouzo region phase diagram boundaries shifted considerably upon drug loading, which can be explained by the increased solubility of the polymer-drug complex. This behavior necessitated a substantial adjustment of polymer concentrations required to produce drug-loaded nanoparticles with characteristics comparable to blank nanoparticles. In conclusion, the use of ouzo diagrams is a beneficial tool to manufacture nanoparticles with specified physicochemical properties by the solvent displacement method. (C) 2010 Elsevier B.V. All rights reserved.
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