Advertisement
Research Article| Volume 41, ISSUE 1, P93-96, February 2018

Download started.

Ok

Novel liposome-based and in situ gelling artificial tear formulation for dry eye disease treatment

  • Duygu Acar
    Correspondence
    Corresponding author.
    Affiliations
    Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Complutense University of Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain
    Search for articles by this author
  • Irene Teresa Molina-Martínez
    Affiliations
    Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Complutense University of Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain

    Sanitary Research Institute of the San Carlos Clinical Hospital (IdISSC) and the Ocular Pathology National Net (OFTARED) of the Institute of Health Carlos III, Calle Profesor Martín Lagos, s/n, 28040 Madrid, Spain
    Search for articles by this author
  • Miguel Gómez-Ballesteros
    Affiliations
    Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Complutense University of Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain

    Sanitary Research Institute of the San Carlos Clinical Hospital (IdISSC) and the Ocular Pathology National Net (OFTARED) of the Institute of Health Carlos III, Calle Profesor Martín Lagos, s/n, 28040 Madrid, Spain
    Search for articles by this author
  • Manuel Guzmán-Navarro
    Affiliations
    Biomedical Sciences Department, Pharmacy and Pharmaceutical Technology Unit, Faculty of Pharmacy, University of Alcalá, Ctra. de Madrid-Barcelona (Autovía A2) Km. 33,600, 28805 Alcalá de Henares, Madrid, Spain
    Search for articles by this author
  • José Manuel Benítez-del-Castillo
    Affiliations
    Sanitary Research Institute of the San Carlos Clinical Hospital (IdISSC) and the Ocular Pathology National Net (OFTARED) of the Institute of Health Carlos III, Calle Profesor Martín Lagos, s/n, 28040 Madrid, Spain

    Ocular Surface and Inflammation Unit, San Carlos Clinical Hospital, Calle Profesor Martín Lagos, s/n, 28040 Madrid, Spain
    Search for articles by this author
  • Rocío Herrero-Vanrell
    Affiliations
    Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Complutense University of Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain

    Sanitary Research Institute of the San Carlos Clinical Hospital (IdISSC) and the Ocular Pathology National Net (OFTARED) of the Institute of Health Carlos III, Calle Profesor Martín Lagos, s/n, 28040 Madrid, Spain
    Search for articles by this author
Published:December 06, 2017DOI:https://doi.org/10.1016/j.clae.2017.11.004

      Highlights

      • A novel liposome-based, in situ gelling artificial tear formulation was developed.
      • Physicochemical properties, in vitro and in vivo tolerance were evaluated.
      • The formulation showed suitable properties for topical ophthalmic administration.
      • Good in vitro and in vivo tolerance was observed.
      • The novel artificial tear may be beneficial in the treatment of dry eye disease.

      Abstract

      Purpose

      Artificial tears are widely used in the treatment of dry eye disease, although current formulations do not closely resemble natural tears. The purpose of this study was the design and characterization of a novel in situ gelling artificial tear formulation, containing both lipid and aqueous components, in order to resemble natural tears and replenish the tear film.

      Methods

      Liposomes, containing phosphatidylcholine, cholesterol, vitamins A and E, were prepared by the thin-film hydration method. The aqueous phase of the formulation was comprised of gellan gum, hydroxypropyl methylcellulose, levocarnitine, electrolytes (sodium chloride and potassium chloride), trehalose, and borates. The artificial tear was characterized in terms of liposome size, pH, surface tension, and viscosity. In vitro tolerance studies were performed in a human epithelial carcinoma cell line (HeLa) and a murine macrophage cell line (J774). In vivo tolerance was assessed in rabbits.

      Results

      Liposomes presented a unimodal distribution with a mean size of 200.1 ± 4.4 nm. The resulting surface tension was 53.4 ± 1.1 mN/m (at 33 °C) and the pH was 7.6 ± 0.1. The viscosity of the formulation presented a mean value of 4.0 ± 0.1 mPa s within the shear rate interval of 200–1000 s−1 at 33 °C. Cell viability remained higher than 90% in both cell lines. No discomfort or clinical signs were observed in rabbits.

      Conclusions

      The liposome-based and in situ gelling artificial tear formulation presented good tolerance and suitable properties for topical ophthalmic administration. It may be beneficial in the treatment of dry eye disease.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Contact Lens and Anterior Eye
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Smith J.A.
        • Albeitz J.
        • Begley C.
        • Caffery B.
        • Nichols K.
        • Schaumberg D.
        • et al.
        The epidemiology of dry eye disease: report of the epidemiology subcommittee of the international dry eye WorkShop (2007).
        Ocul Surf. 2007; 5: 93-107
        • Lemp M.A.
        • Baudouin C.
        • Baum J.
        • Dogru M.
        • Foulks G.N.
        • Kinoshita S.
        • et al.
        The definition and classification of dry eye disease: report of the definition and classification subcommittee of the international dry eye workshop (2007).
        Ocul Surf. 2007; 5: 75-92
        • Miljanović B.
        • Dana R.
        • Sullivan D.A.
        • Schaumberg D.A.
        Impact of dry eye syndrome on vision-related quality of life.
        Am J Ophthalmol. 2007; 143: 409-415
        • Benítez-del-Castillo J.
        • Labetoulle M.
        • Baudouin C.
        • Rolando M.
        • Akova Y.A.
        • Aragona P.
        • et al.
        Visual acuity and quality of life in dry eye disease: proceedings of the OCEAN group meeting.
        Ocul Surf. 2017; 15: 169-178
        • Pflugfelder S.
        • Geerling G.
        • Kinoshita S.
        • Lemp M.A.
        • McCulley J.
        • Nelson D.
        • et al.
        Management and therapy of dry eye disease: report of the management and therapy subcommittee of the international dry eye workshop (2007).
        Ocul Surf. 2007; 5: 163-178
        • Vicario-de-la-Torre M.
        • Herrero-Vanrell R.
        • Benítez-del-Castillo J.M.
        • Molina-Martínez I.T.
        New formulations for dry eye treatment.
        Arch Soc Esp Oftalmol. 2007; 82: 395-396
        • Miller D.
        Measurement of the surface tension of tears.
        Arch Ophthal. 1969; 82: 368-371
        • Nagyová B.
        • Tiffany J.M.
        Components responsible for the surface tension of human tears.
        Curr Eye Res. 1999; 19: 4-11
        • Tiffany J.M.
        The viscosity of human tears.
        Int Ophthalmol. 1991; 15: 371-376
        • Gouveia S.M.
        • Tiffany J.M.
        Human tear viscosity: an interactive role for proteins and lipids.
        Biochim Biophys Acta. 2005; 1753: 155-163
        • Bangham A.D.
        • Standish M.M.
        • Watkins J.C.
        Diffusion of univalent ions across the lamellae of swollen phospholipids.
        J Mol Biol. 1965; 13: 238-252
        • Vicario-de-la-Torre M.
        • Benítez-del-Castillo J.M.
        • Vico E.
        • Guzmán M.
        B. de-las-Heras, R. Herrero-Vanrell, I.T. Molina-Martínez, Design and characterization of an ocular topical liposomal preparation to replenish the lipids of the tear film.
        Investig Ophthalmol Vis Sci. 2014; 55: 7839-7847
        • Liu Y.
        • Peterson D.A.
        • Kimura H.
        • Schubert D.
        Mechanism of cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction.
        J Neurochem. 1997; 69: 581-593
        • Enríquez de Salamanca A.
        • Diebold Y.
        • Calonge M.
        • García-Vazquez C.
        • Callejo S.
        • Vila A.
        • et al.
        Chitosan nanoparticles as a potential drug delivery system for the ocular surface: toxicity, uptake mechanism and in vivo tolerance.
        Invest Ophthalmol Vis Sci. 2006; 47: 1416-1425
        • Milas M.
        • Shi X.
        • Rinaudo M.
        On the physicochemical properties of gellan gum.
        Biopolymers. 1990; 30: 451-464
        • Matsukawa S.
        • Watanabe T.
        Gelation mechanism and network structure of mixed solution of low- and high-acyl gellan studied by dynamic viscoelasticity, CD and NMR measurements.
        Food Hydrocoll. 2007; 21: 1355-1361
        • Chandrasekaran R.
        • Thailambal V.G.
        The influence of calcium ions, acetate and L-glycerate groups on the gellan double-helix.
        Carbohydr Polym. 1990; 12: 431-442
        • Miyoshi E.
        • Takaya T.
        • Nishinari K.
        Rheological and thermal studies of gel-sol transition in gellan gum aqueous solutions.
        Carbohydr Polym. 1996; 30: 109-119
        • Kumar K.
        • Dhawan N.
        • Sharma H.
        • Vaidya S.
        • Vaidya B.
        Bioadhesive polymers: novel tool for drug delivery.
        Artif Cells Nanomed Biotechnol. 2014; 42: 274-283
        • Abelson M.
        • Udell I.
        • Weston J.
        Normal human tear pH by direct measurement.
        Arch Ophthalmol. 1981; 99: 301
        • Yamada M.
        • Mochizuki H.
        • Kawai M.
        • Yoshino M.
        • Mashima Y.
        Fluorophotometric measurement of pH of human tears in vivo.
        Curr Eye Res. 1997; 16: 482-486
        • Yamada M.
        • Kawai M.
        • Mochizuki H.
        • Hata Y.
        • Mashima Y.
        Fluorophotometric measurement of the buffering action of human tears in vivo.
        Curr Eye Res. 1998; 17: 1005-1009
        • Carney L.G.
        • Mauger T.F.
        • Hill R.M.
        Buffering in human tears: pH responses to acid and base challenge.
        Investig Ophthalmol Vis Sci. 1989; 30: 747-754
        • Hill R.
        • Carney L.
        Human tear responses to alkali.
        Invest Ophthalmol Vis Sci. 1980; 19: 207-210
        • Han K.
        • Woghiren O.
        • Priefer R.
        Surface tension examination of various liquid oral, nasal, and ophthalmic dosage forms.
        Chem Cent J. 2016; 10: 1-5