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Topical sustained drug delivery to the retina with a drug-eluting contact lens.
Biomaterials 2019; 217:119285B

Abstract

Intravitreal injections and implants are used to deliver drugs to the retina because therapeutic levels of these medications cannot be provided by topical administration (i.e. eye drops). In order to reach the retina, a topically applied drug encounters tear dilution, reflex blinking, and rapid fluid drainage that collectively reduce the drug's residence time on the ocular surface. Residing under the tears, the cornea is the primary gateway into the eye for many topical ophthalmic drugs. We hypothesized that a drug-eluting contact lens that rests on the cornea would therefore be well-suited for delivering drugs to the eye including the retina. We developed a contact lens based dexamethasone delivery system (Dex-DS) that achieved sustained drug delivery to the retina at therapeutic levels. Dex-DS consists of a dexamethasone-polymer film encapsulated inside a contact lens. Rabbits wearing Dex-DS achieved retinal drug concentrations that were 200 times greater than those from intensive (hourly) dexamethasone drops. Conversely, Dex-DS demonstrated lower systemic (blood serum) dexamethasone concentrations. In an efficacy study in rabbits, Dex-DS successfully inhibited retinal vascular leakage induced by intravitreal injection of vascular endothelial growth factor (VEGF). Dex-DS was found to be safe in a four-week repeated dose biocompatibility study in healthy rabbits.

Authors+Show Affiliations

Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA; Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA; Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA; Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA.Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA; Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA.Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA.Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA; Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA; Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA.Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: daniel.kohane@childrens.harvard.edu.Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA; Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: Joseph_Ciolino@meei.harvard.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31299627

Citation

Ross, Amy E., et al. "Topical Sustained Drug Delivery to the Retina With a Drug-eluting Contact Lens." Biomaterials, vol. 217, 2019, p. 119285.
Ross AE, Bengani LC, Tulsan R, et al. Topical sustained drug delivery to the retina with a drug-eluting contact lens. Biomaterials. 2019;217:119285.
Ross, A. E., Bengani, L. C., Tulsan, R., Maidana, D. E., Salvador-Culla, B., Kobashi, H., ... Ciolino, J. B. (2019). Topical sustained drug delivery to the retina with a drug-eluting contact lens. Biomaterials, 217, p. 119285. doi:10.1016/j.biomaterials.2019.119285.
Ross AE, et al. Topical Sustained Drug Delivery to the Retina With a Drug-eluting Contact Lens. Biomaterials. 2019;217:119285. PubMed PMID: 31299627.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Topical sustained drug delivery to the retina with a drug-eluting contact lens. AU - Ross,Amy E, AU - Bengani,Lokendrakumar C, AU - Tulsan,Rehka, AU - Maidana,Daniel E, AU - Salvador-Culla,Borja, AU - Kobashi,Hidenaga, AU - Kolovou,Paraskevi E, AU - Zhai,Hualei, AU - Taghizadeh,Koli, AU - Kuang,Liangju, AU - Mehta,Manisha, AU - Vavvas,Demetrios G, AU - Kohane,Daniel S, AU - Ciolino,Joseph B, Y1 - 2019/06/21/ PY - 2019/03/26/received PY - 2019/06/07/revised PY - 2019/06/13/accepted PY - 2019/7/13/pubmed PY - 2019/7/13/medline PY - 2019/7/13/entrez KW - Contact lens KW - Dexamethasone KW - Pharmacokinetics KW - Retinal edema KW - Topical drug delivery KW - VEGF SP - 119285 EP - 119285 JF - Biomaterials JO - Biomaterials VL - 217 N2 - Intravitreal injections and implants are used to deliver drugs to the retina because therapeutic levels of these medications cannot be provided by topical administration (i.e. eye drops). In order to reach the retina, a topically applied drug encounters tear dilution, reflex blinking, and rapid fluid drainage that collectively reduce the drug's residence time on the ocular surface. Residing under the tears, the cornea is the primary gateway into the eye for many topical ophthalmic drugs. We hypothesized that a drug-eluting contact lens that rests on the cornea would therefore be well-suited for delivering drugs to the eye including the retina. We developed a contact lens based dexamethasone delivery system (Dex-DS) that achieved sustained drug delivery to the retina at therapeutic levels. Dex-DS consists of a dexamethasone-polymer film encapsulated inside a contact lens. Rabbits wearing Dex-DS achieved retinal drug concentrations that were 200 times greater than those from intensive (hourly) dexamethasone drops. Conversely, Dex-DS demonstrated lower systemic (blood serum) dexamethasone concentrations. In an efficacy study in rabbits, Dex-DS successfully inhibited retinal vascular leakage induced by intravitreal injection of vascular endothelial growth factor (VEGF). Dex-DS was found to be safe in a four-week repeated dose biocompatibility study in healthy rabbits. SN - 1878-5905 UR - https://www.unboundmedicine.com/medline/citation/31299627/Topical_sustained_drug_delivery_to_the_retina_with_a_drug-eluting_contact_lens L2 - https://linkinghub.elsevier.com/retrieve/pii/S0142-9612(19)30384-9 DB - PRIME DP - Unbound Medicine ER -