Development and application of a nanocomposite derived from crosslinked HPMC and Au nanoparticles for colon targeted drug delivery

Abstract

Herein, we report a novel route for the synthesis of a poly(acrylamide) (PAAm) crosslinked hydroxypropyl methyl cellulose/Au nanocomposite where chemically crosslinked HPMC (c-HPMC) works as a reducing agent. At first, the crosslinked polymer was developed by grafting PAAm chains onto the HPMC backbone using ethylene glycol dimethacrylate (EGDMA) crosslinker and potassium persulfate (K₂S₂O₈) initiator. Afterwards, AuNPs have been incorporated in situ on the surface of the crosslinked hydrogel, where the hydrogel itself reduces the tetrachloroauric acid (HAuCl₄) in the reaction medium to form the nanocomposite. Different grades of nanocomposites (c-HPMC/Au) have been synthesized by altering the reaction parameters and the best one was optimized with the help of UV-visible spectroscopy. The nanocomposites synthesized, have been characterized by FTIR spectroscopy, ¹³C NMR spectroscopy, XRD studies, FESEM/EDAX/elemental mapping analyses, HR-TEM analysis and TGA analysis. HR-TEM analysis reveals the uniform distribution of spherical AuNPs on the surface of c-HPMC. Rheological characteristics disclose that the nanocomposite demonstrates higher gel strength than that of the crosslinked polymer, mainly because of the enhanced interactions between the organic matrix and inorganic fillers. The pH responsive behaviour of crosslinked hydrogel/composites has been confirmed by measuring the equilibrium swelling ratio in various buffer solutions (pH 1.2 and 7.4) at 37 °C. Biodegradability of the hydrogel/nanocomposite has been verified using hen egg lysozyme. The synthesized nanocomposite also demonstrates non-cytotoxic behaviour towards human mesenchymal stem cells (hMSCs). The in vitro drug release profiles indicate that both ornidazole and 5-amino salicylic acid (5-ASA) are released from the nanocomposite matrix in a controlled fashion. This confirms that the c-HPMC/Au nanocomposite is likely be an excellent alternative for the controlled release of colonic drugs. The release kinetics and mechanism of ornidazole and 5-ASA from the nanocomposite material has been explained using various linear and non-linear mathematical models.