Eye-Targeted Sustained Delivery of Anti-Inflammatory and Antibiotic Drugs to Injured Eyes
Abstract
Objectives and Rationale of Project: The cornea is the clear dome-shaped structure that comprises the very front of the eye. Injuries to ocular tissues often lead to excessive inflammation, and if this damage is not managed or treated properly, the cornea can scar or thin, leading to diminished vision. In addition, injuries to the cornea are highly susceptible to inflammation and infection. For all these reasons, timely management of post-traumatic corneal inflammation and prophylaxis against infection are among the most important factors to minimize damage to the eye from trauma. The current standards of care in clinical practice are based on high-frequency instillation of several medications, e.g., antibiotics and various anti-inflammatory eyedrops, with complicated regimens. The conventional ophthalmic medications, including eyedrops, gels, suspensions, and ointments, suffer mainly from poor ocular bioavailability (< 5%) upon instillation. The anatomy of the eye and its physiological characteristics, such as rapid tear turnover, all contribute to the highly impenetrable anterior surface. As a result, high doses of the formulations must be administered multiple times per day to achieve therapeutic efficacy, which ultimately lead to a high risk of adverse effects and poor patient compliance. To address the above-mentioned shortcomings of the current standard of care, we have launched a multidisciplinary team between ophthalmic and bioengineering investigators in Boston (Harvard Massachusetts Eye and Ear) and Los Angeles (UCLA Chemical Engineering) to develop a new technology platform in the form of an eyedrop for therapeutic delivery of drugs with very low-frequency dosing. The envisioned new generation of eyedrops will be based on precisely engineered Mucus Targeting Particles (MTPs) with stealth properties to facilitate their penetration and retention on the surface of the eye upon instillation. The applied nanoparticles will be formulated to elute anti-inflammatory or antimicrobial compounds at required therapeutic doses within a defined time period. This new generation eyedrop will (1) be easy to apply, (2) not need shaking before application, and (3) enable a homogenous dispersion of therapeutic drug over the ocular surface at each instillation. To achieve our goal, we will formulate and characterize a new type of actively targeting drug delivery platform based on nano-sized particulate systems with controlled drug release properties (Aim 1). In parallel, we will formulate and characterize a matrix solution in which the particles will be embedded in the format of a final eyedrop product (Aim 2). This solution will further enhance passive retention of particles on the ocular surface upon instillation. Finally, we will test the efficacy of our final product in appropriate ex vivo and in vivo models (Aim 3). The aforementioned steps will enable us to take the technology into the clinic (after Investigational New Drug submission) for applications in humans in the next phase of development. Applicability and Potential Impact for Military and Civilian Populations: Post-trauma ocular inflammation and/or infection is a common cause of vision loss in the general population, and even more so among United States warfighters – ocular trauma accounted for 13% of all body injuries in Operations Iraqi Freedom and Enduring Freedom. Corneal injury, in particular, is very common among active duty and combat personnel: In Operation Iraqi Freedom, 12% of eye injuries involved lacerations of the front of the eye. The costs of eye injuries in the military from 2000-2010 were in excess of $2 billion per year. Often, the most critical factor determining visual prognosis in serious ocular trauma is how quickly and efficiently these injuries are treated. A safe ocular drug delivery platform that can deliver the required amount of drug with low instillation frequency, will lead to better compliance and outcomes and will
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110869
Entities
People
- Nasim Annabi
Organizations
- United States Army
- University of California, Los Angeles