Davidson Scott, Lamprou Dimitrios A, Urquhart Andrew J, Grant M Helen, Patwardhan Siddharth V
Department of Chemical and Process Engineering, University of Strathclyde, 75 Montrose Street, Glasgow G1 1XJ, United Kingdom.
Strathclyde Institute of Pharmacy and Biomedical Sciences (SIPBS), University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, United Kingdom.
ACS Biomater Sci Eng. 2016 Sep 12;2(9):1493-1503. doi: 10.1021/acsbiomaterials.6b00224. Epub 2016 Aug 24.
Development of drug delivery systems (DDS) is essential in many cases to remedy the limitations of free drug molecules. Silica has been of great interest as a DDS due to being more robust and versatile than other types of DDS (e.g., liposomes). Using ibuprofen as a model drug, we investigated bioinspired silica (BIS) as a new DDS and compared it to mesoporous silica (MS); the latter has received much attention for drug delivery applications. BIS is synthesized under benign conditions without the use of hazardous chemicals, which enables controllable in situ loading of drugs by carefully designing the DDS formulation conditions. Here, we systematically studied these conditions (e.g., chemistry, concentration, and pH) to understand BIS as a DDS and further achieve high loading and release of ibuprofen. Drug loading into BIS could be enhanced (up to 70%) by increasing the concentration of the bioinspired additive. Increasing the silicate concentration increased the release to 50%. Finally, acidic synthesis conditions could raise loading efficiency to 62% while also increasing the total mass of drug released. By identifying ideal formulation conditions for BIS, we produced a DDS that was able to release fivefold more drug per weight of silica when compared with MCM-41. Biocompatibility of BIS was also investigated, and it was found that, although ∼20% of BIS was able to pass through the gut wall into the bloodstream, it was nonhemolytic (∼2% hemolysis at 500 μg mL) when compared to MS (10% hemolysis at the same concentration). Overall, for DDS, it is clear that BIS has several advantages over MS (ease of synthesis, controllability, and lack of hazardous chemicals) as well as being less toxic, making BIS a real potentially viable green alternative to DDS.
在许多情况下，药物递送系统（DDS）的开发对于弥补游离药物分子的局限性至关重要。由于二氧化硅比其他类型的药物递送系统（如脂质体）更坚固且用途更广泛，因此作为一种药物递送系统备受关注。我们以布洛芬为模型药物，研究了仿生二氧化硅（BIS）作为一种新型药物递送系统，并将其与介孔二氧化硅（MS）进行了比较；后者在药物递送应用中受到了广泛关注。BIS是在温和条件下合成的，无需使用危险化学品，通过精心设计药物递送系统的配方条件，可以实现药物的可控原位负载。在此，我们系统地研究了这些条件（如化学性质、浓度和pH值），以了解BIS作为一种药物递送系统，并进一步实现布洛芬的高负载和释放。通过增加仿生添加剂的浓度，药物负载到BIS中的量可以提高（高达70%）。增加硅酸盐浓度可使释放量增加到50%。最后，酸性合成条件可将负载效率提高到62%，同时还增加了药物释放的总量。通过确定BIS的理想配方条件，我们制备了一种药物递送系统，与MCM - 41相比，每重量二氧化硅能够释放出多五倍的药物。我们还研究了BIS的生物相容性，发现尽管约20%的BIS能够穿过肠壁进入血液，但与MS相比（相同浓度下溶血率为10%），它是非溶血的（在500μg/mL时溶血率约为2%）。总体而言，对于药物递送系统来说，很明显BIS比MS具有几个优势（易于合成、可控性以及无危险化学品），并且毒性更小，这使得BIS成为一种真正具有潜在可行性的药物递送系统的绿色替代品。
