PMID- 36559244 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20221226 IS - 1999-4923 (Print) IS - 1999-4923 (Electronic) IS - 1999-4923 (Linking) VI - 14 IP - 12 DP - 2022 Dec 8 TI - Topical Sustained Delivery of Miltefosine Via Drug-Eluting Contact Lenses to Treat Acanthamoeba Keratitis. LID - 10.3390/pharmaceutics14122750 [doi] LID - 2750 AB - This study aimed to develop a miltefosine-eluting contact lens (MLF-CL) device that would allow sustained and localized miltefosine release for the treatment of Acanthamoeba keratitis. MLF-CLs were produced in three different miltefosine doses by solvent-casting a thin miltefosine-polymer film around the periphery of a methafilcon hydrogel, which was then lathed into a contact lens. During seven days of in vitro testing, all three formulations demonstrated sustained release from the lens at theoretically therapeutic levels. Based on the physicochemical characterization of MLF-CLs, MLF-CL's physical properties are not significantly different from commercial contact lenses in terms of light transmittance, water content and wettability. MLF-CLs possessed a slight reduction in compression modulus that was attributed to the inclusion of polymer-drug films but still remain within the optimal range of soft contact lenses. In cytotoxicity studies, MLF-CL indicated up to 91% viability, which decreased proportionally as miltefosine loading increased. A three-day biocompatibility test on New Zealand White rabbits revealed no impact of MLF-CLs on the corneal tissue. The MLF-CLs provided sustained in vitro release of miltefosine for a week while maintaining comparable physical features to a commercial contact lens. MLF-CL has a promising potential to be used as a successful treatment method for Acanthamoeba keratitis. FAU - Chen, Lin AU - Chen L AUID- ORCID: 0000-0002-1187-2934 AD - Department of Optometry and Visual Science, West China Hospital, Sichuan University, Chengdu 610041, China. AD - Department of Ophthalmology, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, China. AD - Department of Ophthalmology, Schepens Eye Research Institute of Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA. FAU - Kuang, Liangju AU - Kuang L AUID- ORCID: 0000-0003-1799-6716 AD - Department of Ophthalmology, Schepens Eye Research Institute of Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA. FAU - Ross, Amy E AU - Ross AE AD - Department of Ophthalmology, Schepens Eye Research Institute of Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA. FAU - Farhat, Wissam AU - Farhat W AUID- ORCID: 0000-0002-1050-3723 AD - Department of Ophthalmology, Schepens Eye Research Institute of Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA. FAU - Boychev, Nikolay AU - Boychev N AUID- ORCID: 0000-0003-2674-0835 AD - Department of Ophthalmology, Schepens Eye Research Institute of Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA. FAU - Sharfi, Sina AU - Sharfi S AD - Department of Ophthalmology, Schepens Eye Research Institute of Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA. FAU - Kanu, Levi N AU - Kanu LN AUID- ORCID: 0000-0001-6428-4696 AD - Department of Ophthalmology, Schepens Eye Research Institute of Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA. FAU - Liu, Longqian AU - Liu L AD - Department of Optometry and Visual Science, West China Hospital, Sichuan University, Chengdu 610041, China. FAU - Kohane, Daniel S AU - Kohane DS AD - Department of Anesthesia, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA. FAU - Ciolino, Joseph B AU - Ciolino JB AD - Department of Ophthalmology, Schepens Eye Research Institute of Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA. LA - eng PT - Journal Article DEP - 20221208 PL - Switzerland TA - Pharmaceutics JT - Pharmaceutics JID - 101534003 PMC - PMC9781349 OTO - NOTNLM OT - PLGA OT - acanthamoeba keratitis OT - contact lens OT - controlled drug delivery OT - miltefosine COIS- J.B.C. and D.S.K. have a financial interest in Theroptix, a company developing a contact lens drug delivery system. They are inventors of the technology, co-founders, and serve as consultants. J.B.C.'s interests were reviewed and are managed by Massachusetts Eye and Ear and Mass General Brigham Healthcare in accordance with their conflict of interest policies. D.S.K.'s interests are managed by Boston Children's Hospital in accordance with their conflict of interest policies. EDAT- 2022/12/24 06:00 MHDA- 2022/12/24 06:01 PMCR- 2022/12/08 CRDT- 2022/12/23 01:57 PHST- 2022/10/12 00:00 [received] PHST- 2022/11/18 00:00 [revised] PHST- 2022/11/23 00:00 [accepted] PHST- 2022/12/23 01:57 [entrez] PHST- 2022/12/24 06:00 [pubmed] PHST- 2022/12/24 06:01 [medline] PHST- 2022/12/08 00:00 [pmc-release] AID - pharmaceutics14122750 [pii] AID - pharmaceutics-14-02750 [pii] AID - 10.3390/pharmaceutics14122750 [doi] PST - epublish SO - Pharmaceutics. 2022 Dec 8;14(12):2750. doi: 10.3390/pharmaceutics14122750.