Brunner A, Mäder K, Göpferich A
Aventis Research & Technologies, Industriepark Hoechst, Frankfurt am Main, Germany.
Pharm Res. 1999 Jun;16(6):847-53. doi: 10.1023/a:1018822002353.
To measure changes in pH as well as osmotic pressure in aqueous pores and cavities inside biodegradable microspheres made from polymers such as poly(D,L-lactic acid) (PLA) and poly(D,L-lactic acid -co- glycolic acid) (PLGA).
The internal osmotic pressure inside eroding PLA microspheres was analyzed with differential scanning calorimetry (DSC) in a temperature range of 10 to--25 degrees C. The osmotic pressure was calculated from the melting peaks of the aqueous phase using purity analysis. For pH determination, PLGA microspheres were loaded with a pH-sensitive spin probe which allowed the determination of pH by electron paramagnetic resonance (EPR).
The osmotic pressure in PLA microspheres increased to 600 mOsm within four days and decreased to 400 mOsm after two weeks. The pH in PLGA microspheres in this study was < or =4.7. Basic drugs such as gentamicin free base or buffering additives led to a pH increase. In no case, however, did the internal pH exceed a value of 6 within 13 hours.
DSC and EPR are useful techniques to characterize the chemical microenvironment inside eroding microspheres. This data in combination with detailed information on peptide and protein stability could allow in the future to predict the stability of such compounds within degradable polymers.
测量由聚（D，L-乳酸）（PLA）和聚（D，L-乳酸-共-乙醇酸）（PLGA）等聚合物制成的可生物降解微球内部水相孔隙和腔体内的pH值以及渗透压变化。
采用差示扫描量热法（DSC）在10至25摄氏度的温度范围内分析侵蚀性PLA微球内部的渗透压。使用纯度分析从水相的熔融峰计算渗透压。对于pH值测定，将PLGA微球装载对pH敏感的自旋探针，通过电子顺磁共振（EPR）测定pH值。
PLA微球中的渗透压在四天内增加到600 mOsm，两周后降至400 mOsm。本研究中PLGA微球的pH值≤4.7。庆大霉素游离碱等碱性药物或缓冲添加剂导致pH值升高。然而，在任何情况下，内部pH值在13小时内均未超过6。
DSC和EPR是表征侵蚀性微球内部化学微环境的有用技术。这些数据与关于肽和蛋白质稳定性的详细信息相结合，未来可能有助于预测此类化合物在可降解聚合物中的稳定性。
