Development of a novel bioerodible dexamethasone implant for uveitis and postoperative cataract inflammation

Abstract

Delivery of anti-inflammatory steroids concurrently to both anterior and posterior segments of the eye is a challenge. The anterior ocular structures limit topical delivery. Injection can be disproportionately and repeatedly invasive and selective for only one ocular hemisphere. We developed a novel implant that can compensate for the limited conveyance of topical medicine and reduce the repetitive invasiveness of injection from the capsular bag allowing dexamethasone (DXM) delivery to both the anterior and posterior chambers. To establish proof of concept, microparticles were prepared with PLGA [poly(d,l-lactide-co-glycolide), 50:50, MW. 7000–17000], hydroxypropyl methyl cellulose (HPMC), and DXM by oil-in-water emulsion/solvent evaporation technique. Zeatsizer Nano and SEM (scanning electron microscopy) results showed microspheres in the range of 8 ± 1 μM. The target load of DXM in the microparticles was ~20.0% with a % recovery of 99.9% (w/w). Dose related pharmacokinetics with near zero order kinetics was observed for up to 6 weeks in rabbits with intracapsular bag implants. DXM flow was bidirectional from the endocapsular space and significant concentrations were found in the anterior and posterior chambers after up to 6 weeks. Whereas, with topical drops the exposure was minimal in all the ocular tissues with greater systemic exposure. Intraocular pressure was normal in all of the study groups, slit lamp biomicroscopy examinations revealed that no cells or fibrin formation in the anterior and posterior chamber with implants but flare, cells and fibrin was present in the topical drops group. Histological examination revealed normal tissues and no signs of inflammation in all the groups. The implant did not migrate to the center of the eye or obstruct the visual axis. We believe these findings demonstrate the feasibility of drug delivery from the capsular bag to the anterior and posterior segments effectively compared to topical alternatives.

Topical Ocular Drug Delivery to the Back of the Eye by Mucus-Penetrating Particles

“…[5][6][7] As a result, high systemic doses and/or invasive therapies are used currently to treat a variety of conditions affecting the back of the eye, including sight-threatening diseases, such as age-related macular degeneration (AMD), diabetic retinopathy, and posterior uveitis. [8][9][10][11][12] High systemic dosing provides limited local exposure and duration of action, and often is associated with liabilities and drug-specific toxicities. [1][2] Intravitreal (IVT) injections provide the most direct method of delivery to the posterior tissues; however, IVT injections have the inherent potential for serious adverse events, such as retinal detachment, hemorrhage, endophthalmitis, and the development of cataracts.…”

Effect of an intravitreal dexamethasone device on ocular inflammation after phacoemulsification in dogs

“…Additionally, implantation of the device can cause a small loss of vitreous amount, which act as a compensatory mechanism able to maintain lower values of IOP. Other intraocular dexamethasone-releasing devices used in previous studies have not been found to cause a significant IOP changes (FIAHO et al, 2006(FIAHO et al, , 2007CHENNAMANENI et al, 2013). However, a device containing fluocinolone acetonide has been reported to induce increase in IOP (BOLLINGER et al, 2011).…”

“…This consideration is clinically important because systemic steroid use is associated with many adverse effects. When an intraocular device is used, the systemic exposure to dexamethasone is extremely low (CHENNAMANENI et al, 2013). In fact, it is lower than when topical or systemic steroids are used (WEIJTENS et al, 2002).…”

The role of Dexamethasone in clinical pharmaceutical treatment for patients with cataract surgery

“…Reports have indicated that the efficacy and safety of DEX for patients after cataract surgery and outcomes have showed DEX is potential drug for the prevention and treatment of retinal vein occlusion and non-infectious uveitis (18,19). In addition, DEX management decreased inflammation for uveitis and postoperative cataract inflammation (20). In this study, we investigated the ameliorative effects of DEX in decreasing AC inflammation compared to IND and CIP groups.…”