Abu-Izza K A, Lu D R
Department of Pharmaceutics, College of Pharmacy, University of Georgia, Athens 30602, USA.
Pharm Dev Technol. 1998 Nov;3(4):495-501. doi: 10.3109/10837459809028631.
The purpose of this study was to assess the effect of gastrointestinal proteins on the in vitro release of zidovudine (AZT) from ethylcellulose microspheres, and to investigate protein adsorption as a possible mechanism that mediates this effect. AZT release from ethylcellulose microspheres was tested in the presence of different gastrointestinal proteins, both dietary (casein and albumin) and endogenous (pepsin, pancreatin, and mucin) in simulated gastric fluid and/or simulated intestinal fluid. The resulting release profiles were compared with those produced in the corresponding release media without the presence of proteins. Protein adsorption on AZT-loaded ethylcellulose microspheres was studied for the five proteins under investigation. The amounts of adsorbed proteins were determined by fluorescent spectrometry after the protein solution was reacted with fluoraldehyde reagent. All of the investigated proteins were found to slow the release of AZT from ethylcellulose microspheres. At gastric pH, ovalbumin and casein had the maximum effect on AZT release. Mucin exerted a more pronounced effect at gastric pH compared with that at intestinal pH. The negative effect of pancreatin on AZT release increased when its concentration was increased. The five proteins were found to adsorb on AZT-loaded ethylcellulose microspheres with varying quantities. The observed protein adsorption is believed to cause blockage of the small pores and channels in the microsphere structure, and consequently slow the release of AZT.
本研究的目的是评估胃肠道蛋白质对齐多夫定（AZT）从乙基纤维素微球中的体外释放的影响，并研究蛋白质吸附作为介导这种影响的一种可能机制。在模拟胃液和/或模拟肠液中，在不同的胃肠道蛋白质（包括膳食蛋白质（酪蛋白和白蛋白）和内源性蛋白质（胃蛋白酶、胰酶和粘蛋白））存在的情况下，测试了AZT从乙基纤维素微球中的释放情况。将所得的释放曲线与在相应的无蛋白质释放介质中产生的释放曲线进行比较。研究了所研究的五种蛋白质在载有AZT的乙基纤维素微球上的吸附情况。在蛋白质溶液与氟甲醛试剂反应后，通过荧光光谱法测定吸附的蛋白质的量。发现所有研究的蛋白质均会减缓AZT从乙基纤维素微球中的释放。在胃pH值下，卵清蛋白和酪蛋白对AZT释放的影响最大。与在肠pH值下相比，粘蛋白在胃pH值下对AZT释放的影响更为明显。胰酶浓度增加时，其对AZT释放的负面影响增大。发现这五种蛋白质以不同的量吸附在载有AZT的乙基纤维素微球上。据信观察到的蛋白质吸附会导致微球结构中的小孔和通道堵塞，从而减缓AZT的释放。
