Preparation of alginate-chitosan-cyclodextrin micro- and nanoparticles loaded with anti-tuberculosis compounds

Abstract

This paper describes the synthesis and application of alginate-chitosan-cyclodextrin micro- and nanoparticulate systems loaded with isoniazid (INH) and isoconazole nitrate (ISN) as antimycobacterial compounds. Preparation and morphology of the obtained particles, as well as antimycobacterial activity data of the obtained systems are presented. Docking of isoconazole into the active site of enoyl-acyl carrier protein reductase (InhA) of Mycobacetrium tuberculosis was carried out in order to predict the binding affinity and non-covalent interactions stabilizing the InhA-isoconazole complex. To assess these interactions, frontier molecular orbital calculations were performed for the active site of InhA and isoconazole obtained from docking. Isoconazole was predicted to be an active inhibitor of InhA with the analysis of the molecular docking and electron density distribution. It has been detected that alginate-chitosan-cyclodextrin microparticulate systems loaded with INH and ISN are as effective as pure INH applied in higher dosages.

Keywords: chitosan; density functional theory (DFT); isoconazole; isoniazid; molecular docking; quaternary system; sodium alginate; β-cyclodextrin.

Figure 1

Molecular structures of INH (1) and ISN (2).

Figure 2

SEM micrographs of system 1 particles (top: magnification 331×, bottom: 11770×).

Figure 3

SEM micrographs of system 2 particles (top: magnification 334×, bottom: 5540×).

Figure 4

SEM micrographs of system 3 particles (top: magnification 338×, bottom: 6390×).

Figure 5

SEM micrographs of system 4 particles (top: magnification 326×, bottom: 12480×).

Figure 6

SEM micrographs of system 5 particles (top: magnification 333×, bottom: 9330×).

Figure 7

IR spectra of ISN, β-cyclodextrin, sodium alginate, chitosan, calcium chloride and system 1 (ISN–β-cyclodextrin–alginate–chitosan).

Figure 8

IR spectra of INH, β-cyclodextrin, sodium alginate, chitosan, calcium chloride and system 2.

Figure 9

IR spectra of INH, β-cyclodextrin, sodium alginate, chitosan, calcium chloride and system 3.

Figure 10

IR spectra of INH, β-cyclodextrin, sodium alginate, chitosan, calcium chloride and system 4.

Figure 11

IR spectra of INH, β-cyclodextrin, sodium alginate, chitosan, calcium chloride and system 5.

Figure 12

3D (left) and 2D (right) representation of the isoconazole docking pose in the active site of InhA (PDB code: 4U0J).

Figure 13

3D view of HOMO (a) and LUMO (b) for the InhA active site interacting with isoconazole.