Péan J M, Boury F, Venier-Julienne M C, Menei P, Proust J E, Benoit J P
UPRES EA 2169, Faculté de Pharmacie, Angers, France.
Pharm Res. 1999 Aug;16(8):1294-9. doi: 10.1023/a:1014818118224.
The aim of this work was to understand the mechanism by which co-encapsulated PEG 400 improved the stability of NGF and allowed a continuous release from PLGA 37.5/25 microspheres.
Microparticles were prepared according to the double emulsion method. PEG 400 was added with NGF in the internal aqueous phase (PEG/PLGA ratio 1/1 and 1.8/1). Its effect was investigated through interfacial tension studies. Protein stability was assessed by ELISA.
A novel application of PEG in protein stabilization during encapsulation was evidenced by adsorption kinetics studies. PEG 400 limited the penetration of NGF in the interfacial film of the primary emulsion. Consequently, it stabilized the NGF by reducing the contact with the organic phase. In addition, it avoided the NGF release profile to level off by limiting the irreversible NGF anchorage in the polymer layers. On the other hand, the amount of active NGF released in the early stages was increased. During microparticle preparation, NaCl could be added in the external aqueous phase to modify the structure of microparticles. This allowed to reduce the initial release rate without affecting the protein stability always encountered in the absence of PEG.
PEG 400 appeared of major interest to achieve a continuous delivery of NGF over seven weeks from biodegradable microparticles prepared by the double emulsion technique.
本研究旨在了解共包封的聚乙二醇400（PEG 400）提高神经生长因子（NGF）稳定性并使NGF从聚乳酸-乙醇酸共聚物（PLGA 37.5/25）微球中持续释放的机制。
采用复乳法制备微球。将PEG 400与NGF加入内水相中（PEG/PLGA比例为1/1和1.8/1）。通过界面张力研究考察其作用效果。采用酶联免疫吸附测定（ELISA）法评估蛋白质稳定性。
吸附动力学研究证明了PEG在包封过程中对蛋白质稳定化的新应用。PEG 400限制了NGF渗透到初乳的界面膜中。因此，它通过减少与有机相的接触来稳定NGF。此外，它通过限制NGF在聚合物层中的不可逆锚定，避免了NGF释放曲线趋于平稳。另一方面，早期释放的活性NGF量增加。在微球制备过程中，可在外水相中加入氯化钠来改变微球结构。这能够降低初始释放速率，同时不影响在不存在PEG时始终能保持的蛋白质稳定性。
对于通过复乳技术制备的可生物降解微球，PEG 400对于实现NGF持续七周的递送似乎至关重要。
