Desenvolvimento de miliesferas poliméricas de Quitosana/Alginato contendo [6]-shogaol

Abstract

Chitosan and sodium alginate are used in the production of modified drug-release millispheres. This technology can be used as an alternative to improve the therapeutic efficacy of active substances, such as [6]-shogaol, a natural product found in ginger with antimicrobial potential. The study aimed to develop and evaluate the antimicrobial activity of chitosan/alginate polymeric millispheres cross-linked with genipin and containing [6]-shogaol. [6]-shogaol was obtained after the dehydration reaction of [6]-gingerol, a substance isolated from ginger using conventional chromatographic techniques. The millispheres were prepared by dripping the genipin-cross-linked chitosan gel containing [6]-shogaol into a dispersion of sodium alginate and sodium tripolyphosphate. The millispheres were characterized by optical microscopy, encapsulation efficiency (EE), loading capacity (CC) and swelling index (II). The [6]-shogaol release test was performed at pHs 1.2, 4.5 and 6.8. The stability of [6]-shogaol was evaluated at pHs 4.5 and 6.8. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the active substance were determined against Staphylococcus aureus by broth microdilution and agar plating, respectively. The antimicrobial effect of [6]-shogaol incorporated into the millispheres was determined over time in liquid medium. [6]-shogaol was obtained with 97.5% purity. The millispheres were morphologically uniform with a diameter of 1.48 ± 0.11 mm, EE of 68.1% and CC of 2.5%. The highest II was observed at pH 1.2 (458 ± 43%). The release profiles of free [6]-shogaol and incorporated in polymeric millispheres followed the Weibull, Korsmeyer-Peppas, Peppas-Sahlin, and Logistic release models, revealing that Fickian diffusion was the predominant release mechanism. [6]-shogaol showed greater stability at pH 4.5. The MIC of the active substance was 128 µg/mL, while the MBC was 256 µg/mL. The millispheres containing [6]-shogaol inhibited the growth of S. aureus for 96 hours. Therefore, the polymeric millispheres containing [6]-shogaol were able to prolong the release in the gastric environment in the postprandial condition, preserving the antimicrobial properties, demonstrating their pharmaceutical applicability.