Effect of Poly(vinyl alcohol) on Nanoencapsulation of Budesonide in Chitosan Nanoparticles via Ionic Gelation and Its Improved Bioavailability

Abstract

Chitosan (CS) is a polymer extensively used in drug delivery formulations mainly due to its biocompatibility and low toxicity. In the present study, chitosan was used for nanoencapsulation of a budesonide (BUD) drug via the well-established ionic gelation technique and a slight modification of it, using also poly(vinyl alcohol) (PVA) as a surfactant. Scanning electron microscopy (SEM) micrographs revealed that spherical nanoparticles were successfully prepared with average sizes range between 363 and 543 nm, as were measured by dynamic light scattering (DLS), while zeta potential verified their positive charged surface. X-ray diffraction (XRD) patterns revealed that BUD was encapsulated in crystalline state in nanoparticles but with a lower degree of crystallinity than the neat drug, which was also proven by differential scanning calorimetry (DSC) and melting peak measurements. This could be attributed to interactions that take place between BUD and CS, which were revealed by FTIR and by an extended computational study. An in vitro release study of budesonide showed a slight enhancement in the BUD dissolution profile, compared to the neat drug. However, drug release was substantially increased by introducing PVA during the nanoencapsulation procedure, which is attributed to the higher amorphization of BUD on these nanoparticles. The release curves were analyzed using a diffusion model that allows estimation of BUD diffusivity in the nanoparticles.

Keywords: COPD treatment; budesonide; chitosan nanoparticles; drug dissolution enhancement; drug release; sustain release.

Figure 1

Molecular structures of Budesonide (BUD), chitosan and PVA.

Figure 2

Particle size distribution measured by dynamic light scattering (DLS) of (a) CS-TPP-BUD and (b) CS-TPP-PVA-BUD nanoparticles for three different BUD concentrations, 10, 20 and 30 wt%.

Figure 3

SEM image of: (a) CS-TPP-BUD 10%, (b) CS-TPP-BUD 20%, (c) CS-TPP-BUD 30%, (d) CS-TPP-PVA-BUD 10%, (e) CS-TPP-PVA-BUD 20% and (f) CS-TPP-PVA-BUD 30%.

Figure 4

FTIR spectra of CS nanoparticles containing BUD in different ratios 10%, 20%, 30% w/w.

Figure 5

XRD patterns of CS, BUD and CS nanoparticles containing BUD in different concentrations of 10%, 20%, 30% w/w.

Figure 6

DSC curves of chitosan nanoparticles containing BUD.

Figure 7

TGA thermograms of CS, BUD and chitosan nanoparticles containing BUD (a) without emulsifier and (b) with emulsifier.

Figure 8

The configuration with the strongest interaction between Chitosan and Budesonide has two sites, one for each carbonyl oxygen atom of BUD. Each carbonyl oxygen interacts with the second nearest protonated amino group.

Figure 9

Interaction energy of BUD with CS that has fully protonated amino groups. The inset enlarges the region at the bottom of the energy well. The blue line is a fit of the computed data points to a Mie potential (see main text). Datapoints (solid circles) were computed at the ωB97X-D3(BJ)/def2-TZVP/PCM level of theory.

Figure 10

Experimental (FT-IR) and computed infrared spectra of interacting Chitosan–Budesonide system. The experimental curve (dashed line) corresponds to CS nanoparticles containing 20% w/w BUD. The theoretical curve (solid line) was computed at the B97-D3(BJ)/def2-TZVP/PCM level of theory.

Figure 11

In vitro release of BUD from CS nanoparticles at pH 7.4.

Figure 12

Comparison between experimental (symbols) and model (continuous lines) drug release data for (a) neat BUD (b) CS-TPP-BUD (c) CS-TPP-PVA-BUD.

Figure 12

Comparison between experimental (symbols) and model (continuous lines) drug release data for (a) neat BUD (b) CS-TPP-BUD (c) CS-TPP-PVA-BUD.