Stjern Louise, Voittonen Sandra, Weldemichel Rahel, Thuresson Sofia, Agnes Marco, Benkovics Gabor, Fenyvesi Éva, Malanga Milo, Yannakopoulou Konstantina, Feiler Adam, Valetti Sabrina
KTH, Royal Institute of Technology, SE-100 44 Stockholm, Sweden.
Institute of Nanoscience and Nanotechnology, National Center for Scientific Research "Demokritos", Patr. Grigoriou E' & 27 Neapoleos str., 15341, AgiaParaskevi, Attikis, Greece.
Int J Pharm. 2017 Oct 15;531(2):595-605. doi: 10.1016/j.ijpharm.2017.05.062. Epub 2017 May 26.
Cyclodextrins (CDs) and mesoporous silica particles (MSPs) have been combined as composite carriers for controlled antibiotic release. CDs were employed as "gatekeeper" agents and grafted onto MSPs to retain drug molecules inside the MSP carrier. A variety of CDs (unfunctionalized, positively charged and carboxymethylated) and three different coupling strategies (covalent binding, electrostatic adsorption and inclusion complexation) were systematically investigated for their ability to control the release of two antibiotic drugs, metronidazole and clofazimine. The drugs had significantly different physicochemical properties (metronidazole - small hydrophilic, clofazimine- large hydrophobic). We report for the first time on the encapsulation and characterization of metronidazole-loaded-MSP. Each CD coating strategy reduced the drug release rate in phosphate buffer compared to unmodified MSP (from 20% to 100% retained drug). Covalent binding and inclusion complex approaches were significantly more effective than electrostatically adsorbed CD. In particular, the novel inclusion complex based on host/guest interaction between benzyl-modified silica surface and α-CD proved to be very effective (60-100% retained drug amount). Using pharmaceutical manufacturing processes, our study shows that CD-MSP composites can retain both hydrophobic and hydrophilic antibiotic compounds with potential translation to triggered release formulation targeting bacterial infections in the colon and lower intestine.
环糊精（CDs）和介孔二氧化硅颗粒（MSPs）已被组合作为用于控制抗生素释放的复合载体。环糊精被用作“守门人”试剂并接枝到介孔二氧化硅颗粒上，以将药物分子保留在介孔二氧化硅颗粒载体内。系统地研究了多种环糊精（未官能化的、带正电荷的和羧甲基化的）以及三种不同的偶联策略（共价结合、静电吸附和包合络合）控制两种抗生素药物甲硝唑和氯法齐明释放的能力。这两种药物具有显著不同的物理化学性质（甲硝唑——小的亲水性，氯法齐明——大的疏水性）。我们首次报道了负载甲硝唑的介孔二氧化硅颗粒的包封和表征。与未修饰的介孔二氧化硅颗粒相比，每种环糊精包衣策略都降低了磷酸盐缓冲液中的药物释放速率（药物保留率从20%到100%）。共价结合和包合络合方法比静电吸附的环糊精显著更有效。特别是，基于苄基修饰的二氧化硅表面与α-环糊精之间的主客体相互作用的新型包合络合物被证明非常有效（药物保留量为60 - 100%）。利用药物制造工艺，我们的研究表明，环糊精 - 介孔二氧化硅颗粒复合材料可以保留疏水性和亲水性抗生素化合物，具有向靶向结肠和下肠道细菌感染的触发释放制剂转化的潜力。
