2
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Polymeric Micelles for the Enhanced Deposition of Hydrophobic Drugs into Ocular Tissues, without Plasma Exposure

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Commercial topical ocular formulations for hydrophobic actives rely on the use of suspensions or oil in water emulsions and neither of these formulation modalities adequately promote drug penetration into ocular tissues. Using the ocular relevant hydrophobic drug, cyclosporine A (CsA), a non-irritant ocular penetration enhancer is showcased, which may be used for the formulation of hydrophobic actives. The activity of this penetration enhancer is demonstrated in a healthy rabbit model. The Molecular Envelope Technology (MET) polymer (N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan), a self-assembling, micelle-forming polymer, was used to formulate CsA into sterile filtered nanoparticulate eye drop formulations and the stability of the formulation tested. Healthy rabbits were dosed with a single dose of a MET–CsA (NM133) 0.05% formulation and ocular tissues analyzed. Optically clear NM133 formulations were prepared containing between 0.01–0.1% w/ v CsA and 0.375–0.75% w/ v MET polymer. NM133 0.01%, NM133 0.02% and NM133 0.05% were stable for 28 days when stored at refrigeration temperature (5–6 °C) and room temperature (16–23 °C), but there was evidence of evaporation of the formulation at 40 °C. There was no change in drug content when NM133 0.05% was stored for 387 days at 4 °C. On topical dosing to rabbits, corneal, conjunctival and scleral AUC 0–24 levels were 25,780 ng.h g −1, 12,046 ng.h g −1 and 5879 ng.h g −1, respectively, with NM133 0.05%. Meanwhile, a similar dose of Restasis 0.05% yielded lower values of 4726 ng.h/g, 4813 ng.h/g and 1729 ng.h/g for the drug corneal, conjunctival and scleral levels, respectively. NM133 thus delivered up to five times more CsA to the ocular surface tissues when compared to Restasis. The MET polymer was non-irritant up to a concentration of 4% w/ v. The MET polymer is a non-irritant ocular penetration enhancer that may be used to deliver hydrophobic drugs in optically clear topical ocular formulations.

          Related collections

          Most cited references 28

          • Record: found
          • Abstract: found
          • Article: not found

          The cellular mechanisms of dry eye: from pathogenesis to treatment.

          Dry eye is a complex disease characterized by changes in the ocular surface epithelia related to reduced quality and/or quantity of tears, inflammatory reaction, and impairment of ocular surface sensitivity. It has recently been proposed that increased tear osmolarity represents a main trigger to the altered cellular mechanisms leading to epithelial damage in dry eye. However, dry eye pathogenesis is multifactorial, with cytotoxic inflammatory mediators, altered lacrimal gland secretion and nerve function, squamous metaplasia of the conjunctival epithelium and decrease of goblet cells density, all playing a role in a detrimental loop that perpetuates and worsens damage to the corneal and conjunctival epithelia. Current topical treatments for dry eye patients include the use of lubricants and anti-inflammatory drugs. However, lubricants only improve symptoms temporarily, and chronic use of topical steroids is associated to severe ocular side effects such as cataract and glaucoma. The deeper understanding of the cellular mechanisms that are altered in dry eye is opening novel perspectives for patients and physicians, who are seeking treatments capable not only of improving symptoms but also of restoring the homeostasis of the ocular surface. In this review, we will focus on novel anti-inflammatory agents and on nerve growth factor, a neurotrophin that is altered in dry eye and has been suggested as a main player in the neuroimmune cross-talk of the ocular surface as well as in the stimulation of corneal sensitivity, epithelial proliferation and differentiation, and stimulation of mucin production by goblet cells. J. Cell. Physiol. 228: 2253-2256, 2013. © 2013 Wiley Periodicals, Inc.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            High-frequency topical cyclosporine 0.05% in the treatment of severe dry eye refractory to twice-daily regimen.

            The purpose of this study was to report the efficacy of topical cyclosporine 0.05% at a frequency of 3 to 4 times daily in severe dry eye disease.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Topical cyclosporine A in the treatment of dry eye: a systematic review and meta-analysis.

               Xiao Zhou,  Rui-Li Wei (2014)
              Cyclosporine A (CsA) is considered a potentially effective treatment for dry eye syndrome (DES), which is now one of the most common ocular problems whose exact mechanism is unknown. Because randomized controlled trials (RCTs) reported to date have shown varying results in the efficacy and safety of CsA in different types of DES, we conducted a systematic review and meta-analysis of RCTs on CsA versus placebo in treating DES to evaluate the treatment efficacy and safety of CsA.
                Bookmark

                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Pharmaceutics
                Pharmaceutics
                pharmaceutics
                Pharmaceutics
                MDPI
                1999-4923
                18 May 2021
                May 2021
                : 13
                : 5
                Affiliations
                [1 ]UCL School of Pharmacy, London’s Global University, 29–39 Brunswick Square, London WC1N 1AX, UK; breznikar7@ 123456gmail.com (J.B.); alessandra_zaffalon@ 123456hotmail.it (A.Z.); uchechukwu.odunze.14@ 123456alumni.ucl.ac.uk (U.O.); a.schatzlein@ 123456ucl.ac.uk (A.G.S.)
                [2 ]Nanomerics Ltd. New Bridge Street House, 6th Floor, 2 London Wall Place, London EC2Y 5AU, UK
                Author notes
                Article
                pharmaceutics-13-00744
                10.3390/pharmaceutics13050744
                8157576
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                Categories
                Article

                Comments

                Comment on this article