In vitro stability of poly(D,L-lactide) and poly(D,L-lactide)/poloxamer nanoparticles in gastrointestinal fluids
In vitro stability of poly(D,L-lactide) and poly(D,L-lactide)/poloxamer nanoparticles in gastrointestinal fluids
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DOI：
10.3109/03639049709146156
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发表时间：
1997-01-01
影响因子：
3.4
通讯作者：
Reich, G
中科院分区：
文献类型：
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作者：
Reich, G
通过纳米沉淀法制备了具有各种表面和本体性质的聚（D，L-丙交酯）（PLA）纳米颗粒，并评估了其在37摄氏度模拟胃肠液中的体外物理和化学稳定性。研究了聚合物特性和泊洛沙姆188（POL 188）吸附的影响。物理稳定性之后是视觉外观、穗尺寸和ζ电位测量。通过凝胶渗透色谱法（GPC）分析分子量变化。由于其负zeta电位的急剧下降，不含泊洛沙姆的纳米颗粒在模拟胃液中絮凝，而与聚合物性质无关。它们在无蛋白肠液中的物理稳定性随着PLA的羧基端基浓度的增加而增加，因此，随着它们的负zeta电位的增加而增加。蛋白质在pH 7.5的影响是相当复杂的，表明带负电荷的蛋白质的稳定作用和带正电荷的蛋白质的不稳定作用。泊洛沙姆188吸附空间稳定的纳米颗粒在胃液中的絮凝，无论PLA的特性。PLA/POL 188纳米颗粒在肠液中的物理稳定性受PLA特性的影响。泊洛沙姆188增加了由疏水性PLA组成的纳米颗粒的物理稳定性，与存在的蛋白质无关。然而，对于由具有高含量羧基端基的PLA组成的PLA/POL纳米颗粒，特别是与带正电荷的蛋白质组合，可以观察到逐渐的穗尺寸增加。这种效应最有可能是由于PLA/POL相互作用的减少，这是由位于纳米颗粒表面上的羧基端基的电离引起的，并导致POL 188的构象变化和/或明显的解吸。PLA和PLA/POL纳米粒子的化学稳定性取决于水合聚合物基质的玻璃化转变温度（T-gH）。无法检测到酶的影响。具有T-gH >37 ° C的纳米颗粒在37 ° C下在超过48小时的时间段内在胃液和肠液中化学稳定。
Poly(D, L-lactide) (PLA) nanoparticles of various surface and bulk properties were prepared by a nanoprecipitation procedure and evaluated for their physical and chemical in vitro stability in simulated gastrointestinal fluids of 37 degrees C. The influence of polymer characteristics and poloxamer 188 (POL 188) adsorption was studied. Physical stability was followed by visual appearance, panicle size, and zeta potential measurements. Molecular weight changes were analyzed by gel permeation chromatography (GPC). Due to a sharp decrease in their negative zeta potential, poloxamer-free nanaparticles flocculated in simulated gastric fluid, irrespective of the polymer properties. Their physical stability in protein-free intestinal fluids increased with an increase in carboxy end group concentration of the PLA and thus, with an increase in their negative zetapotential. Protein effects at pH 7.5 were rather complex indicating a stabilizing effect of negatively charged proteins and a destabilizing effect of positively charged proteins. Poloxamer 188 adsorption sterically stabilized the nanoparticles against flocculation in gastric fluid, irrespective of the PLA characteristics. Physical stability of the PLA/POL 188 nanoparticles in intestinal fluids was affected by the PLA characteristics. Poloxamer 188 increased the physical stability of nanoparticles composed of hydrophobic PLA, irrespective of the proteins present. A gradual panicle size increase could however, be observed for PLA/POL nanoparticles composed of PLA with a high content of carboxy end groups, especially in combination with positively charged proteins. This effect is most likely due to a decrease in PLA/POL interactions resulting from the ionization of the carboxy end groups located on the nanoparticle surface and leading to conformational changes and/or a distinct desorption of POL 188. The chemical stability of PLA and PLA/POL nanoparticles depended on the glass transition temperature (T-gH) Of the hydrated polymer matrix. Enzymatic effects could not be detected. Nanoparticles with T-gH >37 degrees C were chemically stable in both gastric and intestinal fluids at 37 degrees C over a time period of more than 48 hr.