Chitosan-Based Films with 2-Aminothiophene Derivative: Formulation, Characterization and Potential Antifungal Activity

Abstract

In this study, films of chitosan and 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile (6CN), a 2-aminothiophene derivative with great pharmacological potential, were prepared as a system for a topical formulation. 6CN-chitosan films were characterized by physicochemical analyses, such as Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray diffraction (XRD), and scanning electronic microscopy (SEM). Additionally, the antifungal potential of the films was evaluated in vitro against three species of Candida (C. albicans, C. tropicalis, and C. parapsilosis). The results of the FTIR and thermal analysis showed the incorporation of 6CN in the polymer matrix. In the diffractogram, the 6CN-chitosan films exhibited diffraction halos that were characteristic of amorphous structures, while the micrographs showed that 6CN particles were dispersed in the chitosan matrix, exhibiting pores and cracks on the film surface. In addition, the results of antifungal investigation demonstrated that 6CN-chitosan films were effective against Candida species showing potential for application as a new antifungal drug.

Keywords: 2-aminothiophene derivative; antifungal activity; chitosan; films.

Figure 1

Structural representation of (A) 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile (6CN); (B) chitosan.

Figure 2

FTIR spectra of 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile (6CN), blank chitosan film (CF), and 6CN-chitosan films with 6CN concentrations of 0.48 mg·mL⁻¹ (F3), 0.80 mg·mL⁻¹ (F5), and 1.28 mg·mL⁻¹ (F8). (▲) C≡N stretching.

Figure 3

Representation of the possible interactions of 6CN with the polymeric matrix.

Figure 4

Differential scanning calorimetric curves of 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile (6CN), blank chitosan film (CF), and 6CN-chitosan films with 6CN concentrations of 0.48 mg·mL⁻¹ (F3), 0.80 mg·mL⁻¹ (F5), and 1.28 mg·mL⁻¹ (F8).

Figure 5

Thermogravimetric curves of 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile (6CN), blank chitosan film (CF), and 6CN-chitosan films with 6CN concentrations of 0.48 mg·mL⁻¹ (F3), 0.80 mg·mL⁻¹ (F5), and 1.28 mg·mL⁻¹ (F8).

Figure 6

X-ray diffraction patterns of 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile (6CN), blank chitosan film (CF), and 6CN-chitosan films with 6CN concentrations of 0.48 mg·mL⁻¹ (F3), 0.80 mg·mL⁻¹ (F5), and 1.28 mg·mL⁻¹ (F8).

Figure 7

SEM micrographs of blank chitosan film at (A) 100× and (B) 500×; of 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile (6CN) at (C) 150× and (D) 500×; of 6CN-chitosan films with 6CN concentration of 0.48 mg·mL⁻¹ (F3) at (E) 100×, (F) 500×, (G) 1000×, and (H) 10,000×; of 6CN-chitosan films with 6CN concentration of 0.80 mg·mL⁻¹ (F5) at (I) 100×, (J) 500×, (K) 1000×, and (L) 10,000×; of 6CN-chitosan films with 6CN concentration of 1.28 mg·mL⁻¹ (F8) at (M) 100×, (N) 500×, (O) 1000×, and (P) 10,000×.

Figure 8

Diameter of the inhibition zones that were caused by 6CN-chitosan films (F3, F5, and F8) against Candida albicans, Candida tropicalis, and Candida parapsilosis. Values were expressed as the mean ± standard error of mean. (n = 3, * p < 0.05).