Reduction in burst release of PLGA microparticles by incorporation into cubic phase-forming systems
Reduction in burst release of PLGA microparticles by incorporation into cubic phase-forming systems
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DOI：
10.1016/j.ejpb.2008.07.008
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发表时间：
2008-11-01
影响因子：
4.9
通讯作者：
Bodmeier, Roland
中科院分区：
文献类型：
--
作者：
Ahmed, Abid Riaz;Dashevsky, Andrei;Bodmeier, Roland
硫代磷酸酯寡核苷酸药物从聚通过将通过w/o/w溶剂萃取/蒸发制备的丙交酯-共-乙交酯（PLGA）微粒掺入以下甘油单油酸酯（GMO）制剂中来减少微粒：1）纯熔融GMO，2）预形成的立方相（GMO +水）或3）低粘度原位立方相形成制剂（GMO +水+共溶剂）。与前两种制剂相比，原位立方相形成制剂具有低粘度，导致微粒的良好分散性和良好的可分散性/可注射性。在与水相接触时，立即形成高度粘性的立方相，从而截留微粒。所有研究的制剂均获得了较低的初始突释和数周内的连续延长释放。共溶剂与原位系统的组合可以很好地控制药物释放。(C)2008 Elsevier B. V.保留所有权利。
A high initial burst release of an phosphorothioate oligonucleotide drug from poly(lactide-co-glycolide) (PLGA) microparticles prepared by the w/o/w solvent extraction/evaporation was reduced by incorporating the microparticles into the following glycerol monooleate (GMO) formulations: 1) pure molten GMO, 2) preformed cubic phase (GMO + water) or 3) low viscosity in situ cubic phase-forming formulations (GMO + water + cosolvent). The in Situ Cubic phase-forming formulations had a low viscosity in contrast to the first two formulations resulting in good dispersability of the microparticles and good syringability/injectability. Upon contact with an aqueous phase, a highly Viscous cubic phase formed immediately entrapping the microparticles. A low initial burst and a continuous extended release over several weeks was obtained with all investigated formulations. The drug release profile could be well controlled by the cosolvent composition with the in situ systems. (C) 2008 Elsevier B.V. All rights reserved.