Novel cyclodextrin-grafted chitosan hydrogel as drug delivery system

BASIGLIO, BRENDA; RIBONE, SERGIO ROMAN; CERUTTI, JUAN PABLO; DE LEGER, WOUT; LONGHI, MARCELA R.; QUEVEDO, MARIO ALFREDO; SMET, MARIO; DEHAEN, WIM; ZOPPI, ARIANA

Rosario

Congreso; 7ma Reunión Internacional de Ciencias Farmacéuticas; 2023

Hydrogels are cross-linked polymer-based materials with a high water content that can be used as a drug delivery system for a wide variety of therapeutic agents. Chitosan, a polyaminosaccharide obtained by alkaline deacetylation of chitin, is widely employed in many applications in thepharmaceutical industry. Among the numerous polymers that can be used for the preparation of hydrogels, chitosan possesses unique properties such as biocompatibility, biodegradability, non-toxicity, mucoadhesion, and antimicrobial activity. Various strategies have been used to chemically modify chitosan in order to add more qualities to the polymer and broaden its potential uses. The chitosan backbone includes amino and hydroxyl groups that provide positions for modifications. Cyclodextrins (CD) are cyclic oligosaccharides extensively employed as solubilizers and stabilizers in pharmaceutical applications because they are capable of forming inclusion complexes. CD grafted onto chitosan backbones is a good alternative since it allows obtaining a polymer that incorporates the capability of CD to form inclusion complexes with different drugs together with the mucoadhesive properties of chitosan.The aim of this study was the synthesis and characterization of a novel β-cyclodextrin-grafted chitosan (CD-f-CS) hydrogel intended to be employed as a drug delivery system. The CD-f-CS hydrogel was synthesized by reductive amination using monoaldehyde-β-CD and hexanone. The successful grafting of β-CD and hexanone onto chitosan was confirmed by Nuclear Magnetic Resonance Spectroscopy (NMR) and Fourier-transform Infrared Spectroscopy (FTIR). NMR was also used to determine the functionalization degree of CD-f-CS, obtaining values of 10% and 4% for β-CD and hexanone, respectively. The TGA thermogram of CD-f-CS revealed thermal degradation at 246 °C. Hydrogel morphology was characterized by SEM, which indicated a porous structure. Swelling studies yielded a swelling ratio of 1881% after 24 hours of water immersion. The in vitro drug release behavior of the hydrogel was studied using rifampicin as a model drug. The hydrogel loading was also confirmed by FTIR due to the presence of a peak at 1254 cm-1, which is related to the C‒O bond stretching vibration of rifampicin. The release profiles showed that mostof the drug (88.0%) was released to the medium within 2 h. In conclusion, a new CD-f-CS polymer was prepared and characterized. The results obtained in these studies indicate that the hydrogel is promising for its potential application as a drug delivery system.