title: 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±1µm. 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.
authors: John A. Moran Eye Center, University of Utah, 65 Mario Capecchi Dr., Salt Lake City, UT 84132, USA.
authors: Srinivas Rao
authors: SR
authors: Chennamaneni
authors: Christina
authors: C
authors: Mamalis
authors: Bonnie
authors: B
authors: Archer
authors: Zack
authors: Z
authors: Oakey
authors: Balamurali K
authors: BK
authors: Ambati
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002386:Cataract / Q000188:drug therapy / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D004343:Drug Implants / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D005123:Eye / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D008863:Microspheres; D010316:Particle Size; D011817:Rabbits; D014605:Uveitis / Q000188:drug therapy / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D004343:Drug Implants; D003907:Dexamethasone