Department of Pharmacognosy, Faculty of Pharmacy, Poznan University of Medical Sciences, Swiecickiego 4, 61-781 Poznan, Poland.
Department of Chemical Technology of Drugs, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznan, Poland.
Int J Mol Sci. 2020 Dec 24;22(1):115. doi: 10.3390/ijms22010115.
Progressive increase in bacterial resistance has caused an urgent need to introduce new antibiotics, one of them being oxazolidinones with their representative tedizolid. Despite the broad spectrum of activity of the parent tedizolid, it is characterized by low water solubility, which limits its use. The combination of the active molecule with a multifunctional excipient, which is cyclodextrins, allows preservation of its pharmacological activity and modification of its physicochemical properties. Therefore, the aim of the study was to change the dissolution rate and permeability through the model membrane of tedizolid by formation of solid dispersions with a cyclodextrin. The research included identification of tedizolid-hydroxypropyl-β-cyclodextrin (tedizolid/HP-β-CD) inclusion complex by thermal method (Differential Scanning Colorimetry), spectroscopic methods (powder X-ray diffraction, Fourier-Transform Infrared spectroscopy), and molecular docking. The second part of the research concerned the physicochemical properties (dissolution and permeability) and the biological properties of the system in terms of its microbiological activity. An increase in the dissolution rate was observed in the presence of cyclodextrin, while maintaining a high permeation coefficient and high microbiological activity. The proposed approach is an opportunity to develop drug delivery systems used in the treatment of resistant bacterial infections, in which, in addition to modifying the physicochemical properties caused by cyclodextrin, we observe a favorable change in the pharmacological potential of the bioactives.
细菌耐药性的逐渐增加导致急需引入新的抗生素,其中之一是恶唑烷酮类药物,其代表药物为替加环素。尽管替加环素的母体具有广泛的活性,但它的水溶性低,这限制了它的应用。将活性分子与多功能赋形剂(即环糊精)结合,可以保持其药理活性并改变其物理化学性质。因此,本研究的目的是通过与环糊精形成固体分散体来改变替加环素的溶解速率和通过模型膜的渗透性。该研究包括通过热法(差示扫描量热法)、光谱法(粉末 X 射线衍射、傅里叶变换红外光谱)和分子对接来鉴定替加环素-羟丙基-β-环糊精(替加环素/HP-β-CD)包合物。研究的第二部分涉及该系统的物理化学性质(溶解和渗透性)和生物性质,即其微生物活性。在存在环糊精的情况下,观察到溶解速率增加,同时保持高渗透系数和高微生物活性。所提出的方法为开发用于治疗耐药细菌感染的药物输送系统提供了机会,在这些系统中,除了由于环糊精而改变物理化学性质外,我们还观察到生物活性的药理潜力发生了有利变化。