Synthesis of calcium-aluminium-ciprofloxacin layered double hydroxide – physicochemical properties and evaluation on antibacterial activity and cytotoxicity / Monica Limau Jadam

• Main Author: Jadam, Monica Limau
• Format: Thesis
• Language: English
• Published: 2021
• Subjects: Metal complexes. Layered double hydroxides
• Online Access: https://ir.uitm.edu.my/id/eprint/61098/1/61098.pdf; https://ir.uitm.edu.my/id/eprint/61098/

Layered double hydroxides (LDHs) have been proposed as drug delivery systems of fluoroquinolones including ciprofloxacin (CPX) to overcome their low bioavailability and prevent the emergence of resistant bacteria. CPX is used in the treatment of various bacterial infections. However, there are cases of side effects associated with CPX such as gastrointestinal irritation, tendon problem and skin cancer. Since these issues have become a major concern in the pharmaceutical industry, more studies on the alteration of drug behaviour were carried out to avoid these harmful side effects. In this study, calcium-aluminium-layered double hydroxide (CAL) carrier with a molar ratio of 3:1 (Ca:Al) was initially synthesized by hydrothermal technique. Subsequently, a fluoroquinolone antibacterial drug, CPX was incorporated into the interlayer of the CAL host by anion exchange method to produce calcium-aluminium-ciprofloxacinlayered double hydroxide (CAC). The successful intercalation was confirmed by powder X-ray diffraction (PXRD) pattern analysis, Fourier transform infrared spectroscopy (FTIR), carbon, hydrogen, and nitrogen analysis (CHN), thermogravimetric and differential thermogravimetic analysis (TGA/DTG), and inductively coupled plasma-atomic emission spectrometry (ICP-AES). The material was also characterized by using field emission scanning electron microscope (FESEM), transmission electron microscopy (TEM), and accelerated surface area and porosity (ASAP) analysis. Well crystallized nanohybrid was obtained at the concentration of 0.2 M CPX. The basal spacing of CAC (0.2 M CPX) synthesized in this study is 17.3 Å, which resulted from the expansion of CAL due to the inclusion of CPX in the interlayer space of the CAL carrier with a loading percentage of 75.9% (w/w). The FTIR spectra of CAC show resemblance to the peaks of CAL and CPX, indicating the inclusion of the drug into the CAL interlayers. The release percentages of the drug into phosphatebuffered saline (PBS) at pH 1.2, pH 4.8, pH 6.8 and 7.4 are 65%, 67%, 58% and 60%, respectively, and are best described by the pseudo-second order kinetic model. Cytotoxicity studies of CPX, CAL and CAC on human lung fibroblast (MRC5) cells and normal mouse embryonic (3T3) cells showed no significant toxicity until 100 μg/mL. The antimicrobial activity of CPX, CAL, and CAC were investigated against Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus by disc diffusion method. All tested treatments were found effective against all tested strains and there is no significant difference between the CPX and CAC as it was similar in their antibacterial activities. The MICs of the synthesized nanocomposite, CAC against Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus were found to be 50, 40, and 60 μg/mL, respectively and the MBCs of the nanocomposite against all the pathogenic bacteria is similar at 5 mg/mL. Therefore, this study proved that CAL nanocarrier can successfully serve as a controlled release and drug delivery system for the antibacterial drug, CPX.