Influence of glyceryl behenate, tripalmitin and stearic acid on the properties of clarithromycin incorporated solid lipid nanoparticles (SLNs): Formulation, characterization, antibacterial activity and cytotoxicity

摘要

Clarithromycin (CLR) is a macrolide derivative which is included in BCS class 2 with low oral bioavailability. Solid lipid nanoparticles (SLNs) have been studied by many researchers for drug application and are very popular systems that continue to be studied. However, the effects of lipids used in SLN production on the formulation properties are one of the few studied topics. Therefore, the aim of this study was to formulate CLR incorporated SLN formulations by 'high-speed homogenization technique" for oral administration and also elucidate the effect of three types of lipid matrix on particle size (PS), polydispersity index (PDI), drug content, release properties etc. For this reason, three types of major lipid matrix (Glyceryl behenate, Tripalmitin and Stearic acid) were chosen in this study. Seven different formulations were characterized in detail and the results were discussed. The PSs of the CLR incorporated SLNs were between 318 and 526 nm. The average PDI of blank nanoparticles varied between 0.211 and 0.409, whereas the average PDI of CLR incorporated SLNs were between 0.228 and 0.472. The drug content was a range of 63-89%. In vitro release studies of SLNs showed extendedrelease up to 48 h after the first 6 h of burst effect. Both the burst effect kinetics and the 48-h release kinetics were investigated. The results showed that the burst effect was fitted to the Korsmeyer-Peppas model and 48 h to the Baker-Lonsdale model. The structures of the formulations were clarified by DSC & FT-IR analysis. The results showed that PS, PDI, drug content and release rates of SLNs were directly related to the carbon chain length of lipid. Antibacterial activity of the formulations was tested against Staphylococcus aureus by microdilution and agar well diffusion methods. Formulations A(3), A(5), A(6) and A(7) rendered CLR, 2 times more effective against its target according to the microdilution method. As for the agar well method, clear zones around A(3), A(5), A(6), and A(7) wells were the same size or larger than clarithromycin zone. The cell viability test was performed with MTT in the NIH 3T3 mouse embryonic fibroblast cell line. At the end of the incubation times, no cell viability differences were observed between CLR and formulations. As a result, in vitro characterization and release data demonstrated the possibility of improved bioavailability of CLR by SLN formulation and the effect of lipid used in this study on formulation characteristics were elucidated in detail. At least in terms of some formulations, improved pharmacodynamic effects were also obtained from antibacterial activity studies.