Controlled release of ciprofloxacin from PLGA-coated contact lenses to treat eye infections
Greenberg, Seth; Linderman, Stephen; Mogilevskaya, Yevgeniya; Weinschenk, Robert
Topical ophthalmic solution, commonly known as eye drops, have long been the most widely-used method for ocular drug delivery. The drug delivery method, however, is characterized pulse delivery to the eye, which results in three consecutive stages: an initial period of overdose, a fairly short period of therapeutic concentration, and an extended period of sub-therapeutic concentration. This problem is further exacerbated by reflex tearing and blinking, which further dilutes and disperses the drop, causing merely 1%-7% of the drug delivered to be absorbed1,2. In recent years, researchers have proposed several designs of drug-eluting contact lenses to address this issue. However, failure to achieve sustained drug release through zero-order release kinetics remains a prevailing problem. An imperative design requirement in an effective drug-eluting contact lens is for the initial burst of release that is characteristic of all mass transfer be followed by a sustained period of nearly constant flux. This allows the drug to remain within a therapeutic concentration range in the eye for a prolonged period of time. Further, the lens must be biocompatible and safe for use. In this study, a contact lens was modeled based on the work of Ciolino et al. to release ciprofloxacin, a common antibiotic for treatment of infections caused by a variety of gram positive and gram negative bacterium, with zero-order release kinetics over many days. COMSOL Multiphysics software was employed to design and stimulate the model within the parameters of commercially available contact lenses. To control for zero-order release, a dual polymer system was used, with an inner polymer film containing ciprofloxacin coated by a transparent polymer commonly used in contact lenses. The former polymer modeled represents poly(lactic-co-glycolic)acid (PLGA), which is biocompatible and has demonstrated ability to control zero-order release kinetics3. This is possible since PLGA degrades with time, maintaining a relatively constant driving force of diffusion despite a finite source of drug. The latter polymer modeled represents pHEMA, which is not biodegradable. By assuming that the radius of the eye is much larger than the contact lens thickness, a two-dimensional, axisymmetric simulation of the system was created with the eye containing the following layers: tear film, epithelium, stroma, and aqueous humor (Figure 1). The model was run with a starting PLGA molecular mass of both 118 kDa and 18 kDa, with initial ciprofloxacin mass of 20mg (1:1 ratio with 118kDa PLGA). Thus, the effect of altering the ratio of drug to PLGA was monitored. The results determined that both 118kDa and 18kDa PLGA show sustained release of ciprofloxacin for one month after a quick initial burst, with the 18kDa PLGA system exhibiting a higher steady state flux. The geometry also proved to be superior, with the design showing a 100% increase in ciprofloxacin concentration in the eye after 50 days over a design with PLGA spanning the width of entire lens. This study thus exhibits prolonged zero-order release kinetics at a therapeutically relevant concentration can be achieved with a contact lens. This prototype can be extended to further applications of ocular drug delivery and have enormous implications in the treatment of eye infections.