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      Systemic anti-inflammatory therapy aided by double-headed nanoparticles in a canine model of acute intraocular inflammation

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          Abstract

          Orally delivered double-headed nanoparticle curcumin has potential to treat intraocular inflammation.

          Abstract

          Novel approaches circumventing blood-ocular barriers in systemic drug delivery are lacking. We hypothesize receptor-mediated delivery of curcumin (CUR) across intestinal and ocular barriers leads to decreased inflammation in a model of lens-induced uveitis. CUR was encapsulated in double-headed polyester nanoparticles using gambogic acid (GA)–coupled polylactide-co-glycolide (PLGA). Orally administered PLGA-GA 2-CUR led to notable aqueous humor CUR levels and was dosed (10 mg/kg twice daily) to adult male beagles ( n = 8 eyes) with induced ocular inflammation. Eyes were evaluated using a semiquantitative preclinical ocular toxicology scoring (SPOTS) and compared to commercial anti-inflammatory treatment (oral carprofen 2.2 mg/kg twice daily) ( n = 8) and untreated controls ( n = 8). PLGA-GA 2-CUR offered improved protection compared with untreated controls and similar protection compared with carprofen, with reduced aqueous flare, miosis, and chemosis in the acute phase (<4 hours). This study highlights the potential of PLGA-GA 2 nanoparticles for systemic drug delivery across ocular barriers.

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          Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel.

          Douglas A Jabs, James T. Rosenbaum, C.Stephen Foster … (2000)
          To provide recommendations for the use of immunosuppressive drugs in the treatment of patients with ocular inflammatory disorders. A 12-person panel of physicians with expertise in ophthalmologic, pediatric, and rheumatologic disease, in research, and in the use of immunosuppressive drugs in patient care. Published clinical study results. Recommendations were rated according to the quality and strength of available evidence. The panel was convened in September of 1999 and met regularly through May 2000. Subgroups of the panel summarized and presented available information on specific topics to the full panel; recommendations and ratings were determined by group consensus. Although corticosteroids represent one of the mainstays in the management of patients with ocular inflammation, in many patients, the severity of the disease, the presence of corticosteroid side effects, or the requirement for doses of systemic corticosteroids highly likely to result in corticosteroid complications supports the rationale for immunosuppressive drugs (for example, antimetabolites, T-cell inhibitors, and alkylating agents) being used in the management of these patients. Because of the potential for side effects, treatment must be individualized and regular monitoring performed. With careful use of immunosuppressive drugs for treatment of ocular inflammatory disorders, many patients will benefit from them either with better control of the ocular inflammation or with a decrease in corticosteroid side effects.
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            Post-cataract prevention of inflammation and macular edema by steroid and nonsteroidal anti-inflammatory eye drops: a systematic review.

            Line Kessel, Britta Tendal, Karsten Juhl Jørgensen … (2014)
            Favorable outcome after cataract surgery depends on proper control of the inflammatory response induced by cataract surgery. Pseudophakic cystoid macular edema is an important cause of visual decline after uncomplicated cataract surgery.
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              An objective evaluation of eyedrop instillation in patients with glaucoma.

              Wendy L. Stone, Alan Robin, Gerald D. Cagle … (2009)
              To evaluate the performance of patients with ocular hypertension and glaucoma who are experienced in the instillation of topical ocular hypotensive medications. We conducted a prospective, open-label study at a single private practice site. We enrolled 139 patients with a diagnosis of glaucoma or ocular hypertension who used 1 or more topical ocular hypotensive medications for at least 6 months and who instilled their own medications. Patients were questioned regarding their use of topical ocular hypotensive medications, and we used a video recording to evaluate patient performance of eyedrop instillation with 2 bottle designs. Patients reported relatively good performance on eyedrop instillation. One hundred twenty-nine of 139 patients (92.8%) reported no problem putting in their eyedrops, and 86 of 139 (61.9%) believed that they never missed their eye when administering the drops. The proportions of patients who were able to instill a single drop into the eye without touching the bottle to the eye were 14 of 64 (21.9%) with a 15-mL bottle and 36 of 117 (30.8%) with a 2.5-mL bottle. Under a single direct observation, patients experienced in the use of topical ocular hypotensive agents performed relatively poorly when instilling a single eyedrop into the eye without touching the bottle tip to the eye or the ocular adnexae. clinicaltrials.gov Identifier: NCT00522600.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Sci Adv
                Journal ID (iso-abbrev): Sci Adv
                Journal ID (publisher-id): SciAdv
                Journal ID (hwp): advances
                Title: Science Advances
                Publisher: American Association for the Advancement of Science
                ISSN (Electronic): 2375-2548
                Publication date Collection: August 2020
                Publication date (Electronic): 26 August 2020
                Volume: 6
                Issue: 35
                Electronic Location Identifier: eabb7878
                Affiliations
                [1 ]Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Reynolds Medical Building, Texas A&M University, Mailstop 1114, College Station, TX, USA.
                [2 ]Department of Small Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX, USA.
                [3 ]Department of Statistics, Texas A&M University, College Station, TX, USA.
                [4 ]Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA.
                Author notes
                [*]

                These authors contributed equally to this work.

                [† ]Corresponding author. Email: mnvrkumar@ 123456tamu.edu (M.N.V.R.K.); escott@ 123456cvm.tamu.edu (E.M.S.); raghu@ 123456tamu.edu (R.G.)
                Author information
                http://orcid.org/0000-0003-0262-5170
                http://orcid.org/0000-0003-3809-3153
                http://orcid.org/0000-0001-8087-6747
                http://orcid.org/0000-0002-9702-7298
                http://orcid.org/0000-0001-5606-401X
                Article
                Publisher ID: abb7878
                DOI: 10.1126/sciadv.abb7878
                PMC ID: 7449680
                PubMed ID: 32923645
                SO-VID: ca9c147d-a06a-4e5a-8459-0268d51e66cd
                Copyright © Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

                History
                Date received : 18 March 2020
                Date accepted : 10 July 2020
                Funding
                Funded by: doi http://dx.doi.org/10.13039/100000053, National Eye Institute;
                Award ID: R01EY028169
                Categories
                Subject: Research Article
                Subject: Research Articles
                Subject: SciAdv r-articles
                Subject: Health and Medicine
                Subject: Health and Medicine
                Custom metadata
                Copyeditor Penchie Limbo

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