New mesalamine polymeric conjugate for controlled release: Preparation, characterization and biodistribution study

作者：Cesar Aina L A; Abrantes Fernanda A; Farah Luana; Castilho Rachel O; Cardoso Valbert; Fernandes Simone O; Araujo Ivana D; Faraco Andre A G^*

来源：European Journal of Pharmaceutical Sciences, 2018, 111: 57-64.

DOI：10.1016/j.ejps.2017.09.037

• Controlled release system
• 5-Aminosalicylic acid
• Chondroitin sulfate
• Scintigraphy
• Technetium-99m

Mesalamine (5-ASA) consists of the first-line therapy for the treatment of ulcerative colitis; however, it has low bioavailability, can cause several systemic adverse events, and has low treatment adherence due to the inconvenient dosing scheme. In this work, a new drug delivery system consisting of chondroitin sulfate linked to 5-ASA was synthesized using a carbodiimide as conjugating agent. The system was characterized by spectroscopic techniques (UV, ATR-FTIR, XRD, and NMR H-1) and thermal analysis (TG/DTG and DSC), suggesting the conjugation between the drug and the polymer. The in vitro release and the corresponding kinetics were also evaluated, revealing that approximately 40% of the drug linked was released at pH 9 for up to 50 h, following Higuchi's model. The conjugate did not show cytotoxicity for the human monocytic cell line at the doses tested, and an in vivo biodistribution study showed that the conjugate remained in the lower GIT for up to 8 h with no uptake in the upper GIT. These data corroborate with the radiation found per segment of GIT and in blood. For this last test the conjugate was radiolabeled with Technetium-99m to allow the scintigraphy evaluation and radiation quantification. In conclusion, the polymeric conjugate was successfully synthesized and demonstrated a mucoadhesiveness on the colon as desired, thus supporting its potential use in the treatment of ulcerative colitis.

• 出版日期2018-1-1