Dadej Adrianna, Woźniak-Braszak Aneta, Bilski Paweł, Piotrowska-Kempisty Hanna, Józkowiak Małgorzata, Stawny Maciej, Dadej Daniela, Mrotek Michał, Jelińska Anna
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznań, Poland.
Functional Materials Physics Division, Faculty of Physics, Adam Mickiewicz University, Uniwersytetu Poznańskiego 2, 61-614 Poznań, Poland.
Materials (Basel). 2022 Jan 26;15(3):946. doi: 10.3390/ma15030946.
Improvement of the bioavailability of poorly soluble medicinal substances is currently one of the major challenges for pharmaceutical industry. Enhancing the dissolution rate of those drugs using novel methods allows to increase their bioavailability. In recent years, silica-based mesoporous materials have been proposed as drug delivery systems that augment the dissolution rate. The aim of this study was to analyse the influence of phenylbutazone adsorption on SBA-15 on its dissolution rate. Moreover, we examined the cytotoxicity of the analyzed silica. The material was characterized by SEM, TEM, DSC, H-NMR, XRD, and FT-IR. The phenylbutazone did not adsorb on unmodified SBA-15, while the adsorption on APTES-modified SBA-15 resulted in 50.43 mg/g of loaded phenylbutazone. Phenylbutazone adsorbed on the APTES-modified SBA-15 was then released in the hydrochloric acidic medium (pH 1.2) and phosphate buffer (pH 7.4) and compared to the dissolution rate of the crystalline phenylbutazone. The release profiles of the amorphous form of adsorbed phenylbutazone are constant in different pH, while the dissolution rate of the crystalline phenylbutazone depends on the pH. The cytotoxicity assays were performed using the Caco-2 cell line. Our results indicate that the analyzed material ensured phenylbutazone adsorption in an amorphous state inside the mesopores and increased its dissolution rate in various pH levels. Furthermore, the cytotoxicity assay proved safety of studied material. Our study demonstrated that APTES-modified SBA-15 can serve as a non-toxic drug carrier that improves the bioavailability of phenylbutazone.
提高难溶性药物的生物利用度是目前制药行业面临的主要挑战之一。使用新方法提高这些药物的溶解速率可以提高它们的生物利用度。近年来，基于二氧化硅的介孔材料已被提议作为提高溶解速率的药物递送系统。本研究的目的是分析苯基布他松在SBA-15上的吸附对其溶解速率的影响。此外，我们还检测了所分析二氧化硅的细胞毒性。该材料通过扫描电子显微镜（SEM）、透射电子显微镜（TEM）、差示扫描量热法（DSC）、氢核磁共振（H-NMR）、X射线衍射（XRD）和傅里叶变换红外光谱（FT-IR）进行表征。苯基布他松不会吸附在未改性的SBA-15上，而在氨基丙基三乙氧基硅烷（APTES）改性的SBA-15上的吸附导致负载的苯基布他松为50.43毫克/克。吸附在APTES改性SBA-15上的苯基布他松随后在盐酸介质（pH 1.2）和磷酸盐缓冲液（pH 7.4）中释放，并与结晶苯基布他松的溶解速率进行比较。吸附的苯基布他松无定形形式的释放曲线在不同pH值下是恒定的，而结晶苯基布他松的溶解速率取决于pH值。使用人结肠腺癌细胞系（Caco-2）进行细胞毒性试验。我们的结果表明，所分析的材料确保了苯基布他松在介孔内以无定形状态吸附，并在不同pH水平下提高了其溶解速率。此外，细胞毒性试验证明了所研究材料的安全性。我们的研究表明，APTES改性的SBA-15可以作为一种无毒的药物载体，提高苯基布他松的生物利用度。
