Controlled release of organic-inorganic nanohybrid:cefadroxil intercalated Zn-Al-layered double hydroxide

Int J Nanomedicine. 2018 May 29:13:3203-3222. doi: 10.2147/IJN.S138840. eCollection 2018.

Abstract

Background: The intercalation of an antibiotic drug, cefadroxil (CD), into the inter-gallery of Zn, Al nitrate-layered double hydroxide (LDH) was accomplished using a co-precipitation method. This formed a nanostructured organic-inorganic hybrid material that can be exploited for the preparation of a controlled release formulation.

Materials and methods: The drug-LDH nanohybrid was characterized by using field emission scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDS), Fourier transform infrared spectroscopy (FTIR) thermogravimetric (TG) analysis, X-ray powder diffraction (XRD) and UV-visible (UV-vis) absorption spectroscopy, which confirmed the intercalation process. Release tests of nanohybrid in the presence or absence of NaCl or poly-acrylamide (PAM) were performed in vitro in gastric (pH 1.2), lysosomal (pH 4.0), intestinal (pH 6.8) and blood (pH 7.4) simulated fluid using UV-vis spectroscopy.

Results: At pH 1.2, LDH was dissolved and intercalated antibiotic released from ZnAl-CD in a molecular form, which led to a significant increase in the antibiotic's solubility. Results showed that the release of drug from nanohybrid at pH 4.0, 6.8 and 7.4 was a sustained process.

Conclusion: This material might reduce side effects by the release of the drug in a controlled manner. However, it was found that the presence of Cl or PAM species in the release media has a negative impact on the release behavior. The weathering mechanism is responsible for the release of CD from the nanocomposite at pH 1.2, while the mechanism of anion exchange may be responsible for the release behavior at pH 4.0, 6.8 and 7.4. A number of kinetic models were chosen to gain more insights into the mechanisms of drug release. At pH 1.2, the zero-order model most satisfactorily explained the release kinetics of CD, while the release data of CD at pH 4.0, 6.8 and 7.4 were governed by Bhaskar kinetics.

Keywords: ZnAl-CD LDH nanohybrid; antibiotic; drug delivery system; drug release; hydrotalcite; kinetics.

MeSH terms

  • Acrylic Resins / chemistry
  • Aluminum / chemistry*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacokinetics
  • Cefadroxil / pharmacokinetics*
  • Delayed-Action Preparations / chemistry
  • Hydrogen-Ion Concentration
  • Hydroxides / chemistry
  • Microscopy, Electron, Scanning
  • Nanocomposites / administration & dosage
  • Nanocomposites / chemistry*
  • Sodium Chloride / chemistry
  • Solubility
  • Spectroscopy, Fourier Transform Infrared
  • Thermogravimetry
  • X-Ray Diffraction
  • Zinc / chemistry*

Substances

  • Acrylic Resins
  • Anti-Bacterial Agents
  • Delayed-Action Preparations
  • Hydroxides
  • Cefadroxil
  • Sodium Chloride
  • polyacrylamide
  • Aluminum
  • Zinc