Role of a novel multifunctional excipient poly(ethylene glycol)-block-oligo(vinyl sulfadimethoxine) in controlled release of lysozyme from PLGA microspheres.
Role of a novel multifunctional excipient poly(ethylene glycol)-block-oligo(vinyl sulfadimethoxine) in controlled release of lysozyme from PLGA microspheres.
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新型多功能赋形剂聚（乙二醇）-嵌段-寡聚（乙烯基磺胺二甲氧嘧啶）在 PLGA 微球中控制溶菌酶释放中的作用。
DOI：
10.1016/j.ijpharm.2008.02.010
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发表时间：
2008
影响因子：
5.8
通讯作者：
Bae,YouHan
中科院分区：
文献类型：
--
作者：
Taluja,Ajay;Bae,YouHan
研究了阴离子聚电解质聚乙二醇-聚乙烯基磺胺二甲氧嘧啶（PEG-OVSDM）和聚乙二醇-聚天冬氨酸（PEG-PAA）与阳离子溶菌酶的离子配对对乳化过程中蛋白质稳定性的影响。暴露于有害界面后的可溶性溶菌酶回收率为42-88%（当与PEG-OVSDM离子配对时，PEG-OVSDM浓度依赖性），而游离溶菌酶仅为30%。PEG-OVSDM比PEG-PAA提供更高的溶菌酶稳定性（36-60%）。当在水相中回收溶菌酶并通过色谱法、酶促测定法、荧光法和质谱法分析时，与溶菌酶标准品相比，溶菌酶未显示出显著的物理化学变化。采用复乳法将溶菌酶引入到聚乳酸-羟基乙酸共聚物（PLGA）微球中。与仅含溶菌酶的对照微球相比，溶菌酶复合物的掺入导致更高的包封效率和装载量，以及更低的不溶性溶菌酶聚集体的发生率。更重要的是，与对照微球的50%相比，离子配对能够将初始溶菌酶释放显著降低至18%，并且提供了对蛋白质释放的总体更好的控制。PEG-PAA在控制释放方面不如PEG-OVSDM有效，这可能是由于该酶与溶菌酶之间的相互作用较弱。这种聚电解质-蛋白质复合的操作可能在蛋白质控制递送中起作用。
This study investigated the effect of ion-pairing of anionic polyelectrolytes: our novel poly(ethylene glycol)-block-oligo(vinyl sulfadimethoxine) (PEG-OVSDM) and poly(ethylene glycol)-block-poly(l-aspartic acid) (PEG-PAA) with cationic lysozyme on retention of protein stability during emulsification. Soluble lysozyme recovery after exposure to the deleterious interface was 42–88% (when ion-paired with PEG-OVSDM, PEG-OVSDM concentration dependent) compared to only 30% for free lysozyme. PEG-OVSDM provided a higher stabilization of lysozyme than PEG-PAA (36–60%). Lysozyme when recovered in the aqueous phase and analyzed by chromatography, enzymatic assay, fluorescence, and mass spectrometry showed no significant physicochemical change when compared with a lysozyme standard. Lysozyme was incorporated into poly(lactide-co-glycolide) (PLGA) microspheres via the typical double emulsion method. Incorporation of lysozyme complexes led to a higher encapsulation efficiency and loading amount, and a lower incidence of insoluble lysozyme aggregates compared to the control microspheres containing lysozyme only. More significantly, ion-pairing was able to dramatically reduce the initial lysozyme release to 18% compared with 50% from control microspheres and provided an overall better control of protein release. PEG-PAA was less effective than PEG-OVSDM in controlling the release probably due to weaker interactions between this polyelectrolyte and lysozyme. Manipulation of such polyelectrolyte–protein complexation may play a role in protein-controlled delivery.