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 accessOne-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 EyeAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- The epidemiology of dry eye disease: report of the epidemiology subcommittee of the international dry eye WorkShop (2007).Ocul Surf. 2007; 5: 93-107
- 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
- Impact of dry eye syndrome on vision-related quality of life.Am J Ophthalmol. 2007; 143: 409-415
- Visual acuity and quality of life in dry eye disease: proceedings of the OCEAN group meeting.Ocul Surf. 2017; 15: 169-178
- 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
- New formulations for dry eye treatment.Arch Soc Esp Oftalmol. 2007; 82: 395-396
- Measurement of the surface tension of tears.Arch Ophthal. 1969; 82: 368-371
- Components responsible for the surface tension of human tears.Curr Eye Res. 1999; 19: 4-11
- The viscosity of human tears.Int Ophthalmol. 1991; 15: 371-376
- Human tear viscosity: an interactive role for proteins and lipids.Biochim Biophys Acta. 2005; 1753: 155-163
- Diffusion of univalent ions across the lamellae of swollen phospholipids.J Mol Biol. 1965; 13: 238-252
- 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
- Mechanism of cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction.J Neurochem. 1997; 69: 581-593
- 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
- On the physicochemical properties of gellan gum.Biopolymers. 1990; 30: 451-464
- 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
- The influence of calcium ions, acetate and L-glycerate groups on the gellan double-helix.Carbohydr Polym. 1990; 12: 431-442
- Rheological and thermal studies of gel-sol transition in gellan gum aqueous solutions.Carbohydr Polym. 1996; 30: 109-119
- Bioadhesive polymers: novel tool for drug delivery.Artif Cells Nanomed Biotechnol. 2014; 42: 274-283
- Normal human tear pH by direct measurement.Arch Ophthalmol. 1981; 99: 301
- Fluorophotometric measurement of pH of human tears in vivo.Curr Eye Res. 1997; 16: 482-486
- Fluorophotometric measurement of the buffering action of human tears in vivo.Curr Eye Res. 1998; 17: 1005-1009
- Buffering in human tears: pH responses to acid and base challenge.Investig Ophthalmol Vis Sci. 1989; 30: 747-754
- Human tear responses to alkali.Invest Ophthalmol Vis Sci. 1980; 19: 207-210
- Surface tension examination of various liquid oral, nasal, and ophthalmic dosage forms.Chem Cent J. 2016; 10: 1-5
Article info
Publication history
Published online: December 06, 2017
Accepted:
November 28,
2017
Received in revised form:
November 22,
2017
Received:
July 5,
2017
Identification
Copyright
© 2017 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.
