Schaefer M J, Singh J
Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo, ND 58105, USA.
AAPS PharmSciTech. 2000 Nov 13;1(4):E32. doi: 10.1208/pt010432.
The purpose of this paper was to study the effect of the isopropyl myristic acid ester (IPM) on the physicochemical characteristics of etoposide-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres-specifically, the effects on the size and drug loading of the microspheres, the polymer matrix and surface morphology, and the release of etoposide from the microspheres. The experiment was structured to examine 2 IPM concentrations (25% and 50%) and 1 control (no IPM) at 2 different etoposide-loading percentages (10% and 5%). The microspheres were prepared using a single-emulsion solvent-extraction procedure. Samples from each batch of microspheres were then analyzed for size distribution, drug-loading efficiency, surface characteristics, in vitro release, and in vitro microsphere degradation. The incorporation of 50% IPM significantly increased (P <.05) the size of the microspheres when compared with the control and 25% IPM microspheres. However, incorporation of 25% or 50% IPM did not change (P >.05) the drug-loading efficiency in comparison with the microspheres prepared without IPM. The microspheres containing 50% IPM were shown to significantly increase (P <.05) the release of etoposide from the microspheres at both etoposide concentrations. The microspheres prepared incorporating 25% IPM and 5% etoposide increased the in vitro release (P <.05) in comparison with the microspheres prepared without IPM. The 5% etoposide-PLGA microspheres showed a smooth, nonporous surface that changed to a dimpled, nonporous surface after addition of 25% IPM. During the in vitro degradation study, the IPM-containing microspheres slowly became porous but retained their structural integrity throughout the experiment.
本文旨在研究肉豆蔻酸异丙酯（IPM）对载有依托泊苷的聚乳酸-乙醇酸共聚物（PLGA）微球物理化学特性的影响，具体包括对微球尺寸、载药量、聚合物基质和表面形态的影响，以及依托泊苷从微球中的释放情况。实验设计了2种IPM浓度（25%和50%）和1个对照组（无IPM），依托泊苷的载药百分比有2种（10%和5%）。微球采用单乳液溶剂萃取法制备。然后对每批微球样品进行尺寸分布、载药效率、表面特性、体外释放和体外微球降解分析。与对照组和含25% IPM的微球相比，加入50% IPM显著增加了微球尺寸（P <.05）。然而，与未添加IPM制备的微球相比，加入25%或50% IPM并未改变载药效率（P >.05）。在两种依托泊苷浓度下，含50% IPM的微球均显示出依托泊苷从微球中的释放显著增加（P <.05）。与未添加IPM制备的微球相比，加入25% IPM和5%依托泊苷制备的微球体外释放增加（P <.05）。5%依托泊苷-PLGA微球表面光滑无孔，加入25% IPM后变为有凹坑的无孔表面。在体外降解研究中，含IPM的微球逐渐变得多孔，但在整个实验过程中保持其结构完整性。
