Purchase this article with an account.
MaryJane Rafii, Barbara Wirostko, Glenwood G Gum, Kayla Godfrey, Hee-Kyoung Lee; Safety, Tolerability, of Ocular Sustained -Release (SR) Moxifloxacin (MX) Hydrogel Films in New Zealand White (NZW) Rabbits for Corneal Ulcers. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4704.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Corneal ulcers, an ocular emergency and a leading cause of blindness globally, require topical fortified compounded off label antibiotics and/or approved fluoroquinolones every hour round the clock for several days to prevent corneal vision loss. Corneal ulcers result from inappropriate contact lens wear, trauma, and persistent corneal epithelial defects secondary to severe dry eye, neurotrophic/diabetic keratitis, and chemical damage. Jade is developing a topical hydrogel/hyaluronic acid (HA) film to deliver MX in a SR manner to overcome the hourly dosing challenges of treating these ulcers. Safety, tolerability, retention of these films on ocular tissue, and resulting MX levels were evaluated in NZW for further product development.
With IACUC-approval NZW (n=24) had their nictitating membranes (NM) removed 3 weeks prior to film placement. NZWs were divided into groups of 6 for each of 4 time points (Day 1, 3, 5 & 7). Two groups (n=3) received one of 2 MX doses (30 or 100 µg) formulated within 6 mm dried biodegradable crosslinked HA Hystem films placed in the inferior cul de sac of right eyes; left eyes served as control (blank film or nothing). Rabbits were restrained, the lower fornix exposed and the films manually placed against the lower bulbar conjunctiva. McDonald-Shadduck scores, clinical exams and body weights were checked daily. Slit lamp photos noted the film placement and retention. Six animals were sacrificed at each of the time points with ocular tissue, tears, and aqueous collected through Day 5 to determine drug release. Films were removed prior to enucleating and analyzed for residual drug levels. Histopathology was performed in a masked manner.
Films were easy to insert without anesthesia. Days 1-7 showed excellent safety and tolerability of the films with normal clinical exams and McDonald-Shadduck scores. The films remained in place through day 5 in select rabbits. By day 7 these bioerodible films were no longer present due to enzymatic degradation by hyaluronidase as well as frictional force.
SR MX films were well tolerated with good retention when placed in the NZW lower cul de sac. This NM removed model is useful for evaluating topically placed SR films and allows for further evaluation of this product as well as using this hydrogel film to release other topical agents in a SR manner.
This PDF is available to Subscribers Only