Fabrication of bioactive rifampicin loaded κ-Car-MA-INH/Nano hydroxyapatite composite for tuberculosis osteomyelitis infected tissue regeneration

Int J Pharm. 2019 Jun 30:565:543-556. doi: 10.1016/j.ijpharm.2019.05.035. Epub 2019 May 15.

Abstract

Biocompatible polymers and ceramic materials have been identified as vital components to fabricate drug delivery and tissue engineering applications because of their high drug loading capability, sustained release and higher mechanical strength with remarkable in-vivo bioavailability. In the present work, initially we designed κ-carrageenan grafted with maleic anhydride and then reacted it with isoniazid drug (κ-Car-MA-INH). The polymeric system was cross linked with nanohydroxyapatite (NHAP) via electrostatic interaction followed by the addition of rifampicin (RF) and loaded to fabricate κ -Car-MA-INH/NHAP/RF nanocomposites. The chemical modification and interaction of drug with the polymeric-ceramic system were characterised by Fourier Transform Infrared spectroscopy (FT-IR). The zeta potential of the κ -Car-MA-INH/NHAP/RF nanocomposite was observed to be -20.04 mV using Zetasizer. The in vitro drug release studies demonstrated that the nanocomposite releases 76% of RF and 82% of INH in 12 days at pH 5.5. Scanning Electron Microscope analysis revealed the structural deformation of Staphylococcus aureus and Klebsiella pneumoniae upon treatment with this nanocomposite. By using ex-vivo studies combined with physio-chemical characterization methods on the erythrocytes, L929 and MG-63 cell lines, this composite was found to be biocompatible, non-cytotoxic and inducing cell proliferation with less significant hemolysis. Thus, our modified drug delivery nanocomposites afforded higher drug bioavailability with large potential for fabrication as long-acting drug delivery nanocomposites, especially with hydrophobic drugs inducing the growth of osteoblastic bone cells.

Keywords: Biocompatible; Bone tuberculosis; Cell proliferation; Hydrophobic drug; Nanohydroxyapatite.

MeSH terms

  • Animals
  • Antitubercular Agents* / administration & dosage
  • Antitubercular Agents* / chemistry
  • Carrageenan / administration & dosage
  • Carrageenan / chemistry
  • Cell Line
  • Drug Delivery Systems*
  • Drug Liberation
  • Durapatite* / administration & dosage
  • Durapatite* / chemistry
  • Erythrocytes / drug effects
  • Hemolysis / drug effects
  • Humans
  • Isoniazid* / administration & dosage
  • Isoniazid* / chemistry
  • Klebsiella pneumoniae / drug effects
  • Macrophages / drug effects
  • Maleic Anhydrides / administration & dosage
  • Maleic Anhydrides / chemistry
  • Mice
  • Nanocomposites* / administration & dosage
  • Nanocomposites* / chemistry
  • Osteoblasts / drug effects
  • Osteomyelitis / drug therapy
  • Regeneration
  • Rifampin* / administration & dosage
  • Rifampin* / chemistry
  • Staphylococcus aureus / drug effects
  • Tuberculosis / drug therapy

Substances

  • Antitubercular Agents
  • Maleic Anhydrides
  • Carrageenan
  • Durapatite
  • Isoniazid
  • Rifampin