Development of mucoadhesive methacrylic anhydride-modified hydroxypropyl methylcellulose hydrogels for topical ocular drug delivery

Abstract

Oxidative stress is a key factor involved in the development and progression of glaucoma. Curcumin is a natural phenolic compound with antioxidant and ant-inflammatory properties. Due to the ocular physiological and anatomical barriers, conventional eye drops with low ocular bioavailability and high dosing frequency remain challenges in ophthalmic drug delivery. Hydroxypropyl methylcellulose (HPMC) is a hydrophilic polymer and has been widely used as an ocular lubricant. In the study, methacrylated HPMC (HPMC-MA) hydrogels were developed for curcumin delivery. The synthesis processes of HPMC-MA were characterized by Fourier transform infrared spectrophotometer and nuclear magnetic resonance spectrometer. The results of rheological analysis revealed that methacrylation of HPMC could increase the bioadhesive force and exhibit the shear-thinning and self-recovery behaviors. Optimal concentration of curcumin and in-vitro biocompatibility of HPMC-MA were evaluated by cell viability of corneal epithelial cells. The optimized HPMC-MA containing 20 μM of curcumin (HMC) with sustained drug release properties could decrease the oxidative damage in trabecular meshwork cells via decrease of the inflammation and apoptosis. In-vivo biocompatibility of topical administration of HMC was demonstrated in rabbits. The results suggested that HMC with sustained drug release and mucoadhesive properties might has potential in the treatment of glaucoma.