title: Synergistic Cysteamine Delivery Nanowafer as an Efficacious Treatment Modality for Corneal Cystinosis.
abstract: A synergy between the polymer biomaterial and drug plays an important role in enhancing the therapeutic efficacy, improving the drug stability, and minimizing the local immune responses in the development of drug delivery systems. Particularly, in the case of ocular drug delivery, the need for the development of synergistic drug delivery system becomes more pronounced because of the wet ocular mucosal surface and highly innervated cornea, which elicit a strong inflammatory response to the instilled drug formulations. This article presents the development of a synergistic cysteamine delivery nanowafer to treat corneal cystinosis. Corneal cystinosis is a rare metabolic disease that causes the accumulation of cystine crystals in the cornea resulting in corneal opacity and loss of vision. It is treated with topical cysteamine (Cys) eye drops that need to be instilled 6-12 times a day throughout the patient's life, which causes side effects such as eye pain, redness, and ocular inflammation. As a result, compliance and treatment outcomes are severely compromised. To surmount these issues, we have developed a clinically translatable Cys nanowafer (Cys-NW) that can be simply applied on the eye with a fingertip. During the course of the drug release, Cys-NW slowly dissolves and fades away. The in vivo studies in cystinosin knockout mice demonstrated twice the therapeutic efficacy of Cys-NW containing 10 μg of Cys administered once a day, compared to 44 μg of Cys as topical eye drops administered twice a day. Furthermore, Cys-NW stabilizes Cys for up to four months at room temperature compared to topical Cys eye drops that need to be frozen or refrigerated and still remain active for only 1 week. The Cys-NW, because of its enhanced therapeutic efficacy, safety profile, and extended drug stability at room temperature, can be rapidly translated to the clinic for human trials.
authors: Department of Ophthalmology, Baylor College of Medicine , Houston, Texas 77054, United States.
authors: Daniela C
authors: DC
authors: Marcano
authors: Department of Ophthalmology, Baylor College of Medicine , Houston, Texas 77054, United States.
authors: Crystal S
authors: CS
authors: Shin
authors: Department of Ophthalmology, University of California , Irvine, California 92697, United States.
authors: Briana
authors: B
authors: Lee
authors: Department of Ophthalmology, Baylor College of Medicine , Houston, Texas 77054, United States.
authors: Lucas C
authors: LC
authors: Isenhart
authors: Metabolomics Core Facility, Baylor College of Medicine , Houston, Texas 77054, United States.
authors: Xing
authors: X
authors: Liu
authors: Metabolomics Core Facility, Baylor College of Medicine , Houston, Texas 77054, United States.
authors: Feng
authors: F
authors: Li
authors: Department of Ophthalmology, University of California , Irvine, California 92697, United States.
authors: James V
authors: JV
authors: Jester
authors: Department of Ophthalmology, Baylor College of Medicine , Houston, Texas 77054, United States.
authors: Stephen C
authors: SC
authors: Pflugfelder
authors: Department of Ophthalmology, University of California , Irvine, California 92697, United States.
authors: Jennifer
authors: J
authors: Simpson
authors: Department of Ophthalmology, Baylor College of Medicine , Houston, Texas 77054, United States.
authors: Ghanashyam
authors: G
authors: Acharya
mesh_terms: D000818:Animals; D003315:Cornea / Q000187:drug effects / Q000378:metabolism*; D003543:Cysteamine / Q000008:administration & dosage* / Q000627:therapeutic use*; D003553:Cystine / Q000378:metabolism; D003554:Cystinosis / Q000188:drug therapy* / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D009883:Ophthalmic Solutions; D003553:Cystine; D003543:Cysteamine
keywords: Nanowafer; corneal cystinosis; cysteamine; drug delivery