Thermosensitive hexanoyl glycol chitosan-based ocular delivery system for glaucoma therapy.

UNLABELLED: Conventional eye drops quickly move away from the surface of the eye; as a result, ocular bioavailability is very limited. To overcome this issue, we developed a thermosensitive hexanoyl glycol chitosan (HGC) as a carrier for topical drug delivery to the eye. Here, we modulated the degree of N-hexanoylation to control the thermogelling behavior and prepared a new ocular formulation of HGC for glaucoma therapy. The viscosity of the aqueous formulation sharply and significantly increases at body temperature. The results from cytotoxicity evaluation showed that HGC is non-toxic at up to 1.25wt.%. In vivo experiments demonstrated that HGC is maintained on the preocular surface for a comparatively longer period of time due to its enhanced viscosity at body temperature. As a result, when brimonidine was loaded, the formulation exhibited attractive bioavailability properties as well as more prolonged period of lowered intra-ocular pressure (14h) compared with Alphagan P, the marketed medication for brimonidine treatment.

STATEMENT OF SIGNIFICANCE: In this manuscript, hexanoyl glycol chitosan (HGC) was synthesized by the N-hexanoylation of glycol chitosan. We have observed that an aqueous solution of HGC exhibited a dramatic increase in viscosity as the temperature increased. The HGC-based formulation showed prolonged retention on the preocular surface and enhanced drug availability and efficacy.