Synthesis and characterization of a novel pH-controllable composite hydrogel for anticancer drug delivery

Abstract

A novel pH-sensitive composite hydrogel (CH) namely 2-Acrylamido-2-methylpropane sulfonic acid (AMPS) grafted N-maleoylchitosan (MACTS) intercalated montmorillonite has been synthesized by in situ intercalation graft copolymerization of AMPS with MACTS intercalated MMT (MACTS/MMT) by using potassium persulfate (KPS) as a free radical initiator, in the presence of N,N-methylenebisacrylamide (MBA) as a crosslinking agent. A hydrophilic anticancer drug, 5-fluorouracil (5-FLU), has been chosen to investigate the loading and release properties of the CH. The CH formation and 5-FLU loading ability of CH have been confirmed by FTIR. X-Ray diffraction (XRD) analysis supports the intercalation reaction of MACTS with MMT, since after intercalation reaction there is an increase in basal spacing. A scanning electron microscopy (SEM) image of drug loaded CH shows a smoother surface whereas blank CH has a cracked and rough surface, this reveals the high affinity of 5-FLU to CH. The encapsulation efficiency of CH reaches the maximum value of 94.0% with CH prepared using 4.0 g of MACTS/MMT, 1.5 g of AMPS, 0.75 g of MBA and 75.0% of drug loading. Swelling profiles obtained show that the CH swelling rate increases with increase of pH up to 6.4 and then starts to decrease. Release profiles of 5-FLU from CH have been studied under both simulated gastric and intestinal pH conditions. The results obtained show that the release rate of the loaded drug molecules was slow at pH 2.4 but increased significantly at pH 7.4. The cell viability test displayed that the 5-FLU loaded CH exhibited an enhanced cell inhibition than that of pure 5-FLU. The studies described in the paper demonstrate the potential viability of a pH-sensitive CH carrier for colon specific anticancer drugs.