Intercalação do antibiótico ciprofloxacino em hidróxido duplo lamelar: caracterização e estudo de liberação in vitro

Abstract

Layered double hydroxides (HDLs) have received great attention in the development of drug delivery systems because of the ability of these inorganic solids to interleave biologically active substances in their region. HDL can be synthesized in the laboratory by simple routes and low cost, which allow the synthesis of high purity solids. There is great concern about antibiotics due to the increased incidence of drug resistant microorganisms currently available for antibiotic therapy. Controlled drug delivery mediated by nanoparticles enables the improvement of therapeutic index, decrease in dose and frequency of administration, increase drug entry into the intracellular environment, better target organ accumulation and limitation of side effects. In this context, the present work aimed to develop the process of synthesis of a lamellar matrix for the intercalation of an antibacterial ciprofloxacin (CIP) and antimicrobial susceptibility tests (TSA) in vitro. For this, the synthesis by mechanochemical route of Zn2 + and Al3 +, which originated the ZnAlHDL matrix, was carried out. Intercalation of CIP was performed by the reconstruction method to obtain an intercalation compound (ZnAlHDL / CIP). The materials obtained were characterized by X-ray diffraction (XRD), infrared (IR) and ramam spectroscopy, thermogravimetric (TG), differential thermal analysis (DTA), scanning electron microscopy (SEM) HAS). The follow-up of the antibiotic release process occurred through TSA by agar-diffusion in disks and wells, minimum inhibitory concentration (MIC) determination and time-kill assay. When the study of the influence of the ratio to obtain the HDL, the ratio of 1.85 showed a structure with DRX pattern characteristic of lamellar material, good crystallinity and basal spacing of 7.57 Å. The IR and Raman spectra indicated the bands associated with the desired constituents in the synthesized HDL. Thermal analysis showed that ZnAlHDL presents the four thermal decomposition events reported in the literature. And the results obtained by MEV and HR-TEM showed that the compounds presented a strong tendency to agglomeration. After the reconstruction method for antibiotic intercalation, there was an increase in basal spacing and displacement of the peak referring to plane (003) to lower angles (2θ), indicating success in the process. During TSA, ZnAlHDL was shown to be a good carrier of ciprofloxacin. Nanohybrid had a better therapeutic index than commercial ciprofloxacin hydrochloride (ATB / CDC). Drug release tests have shown that the drug release system by ZnAlHDL / CIP is sustained, with permanent activity in well diffusion for 96 hours. Compared to ATB / CDC, it had a specific bacterial death rate of 0.364 h-1 (ATB / CIP) and 0.291 h-1 (ZnAlHDL / CIP). Minimum effective bactericidal effect time of 22'40 "and 17'46" of 24-120h. Direct cell count from viable cells 0 to 120 hours, showed complete inhibition of bacterial growth by the ZnAlHDL / CIP and ATB / CDC samples. It can be concluded that HDL is efficient as a carrier of the drug.