Design and characterization of an ocular topical liposomal preparation to replenish the lipids of the tear film.
OBJECTIVE
Dry eye (DE) includes a group of diseases related to tear film disorders. Current trends for DE therapy focus on providing lipid components to replace the damaged lipid layer. Formulations that contain aqueous and mucin-like compounds may have additional therapeutic benefits for DE patients. The aim of this work was to design and evaluate novel formulations having the potential to become topical treatment for DE.


METHODS
Unpreserved liposomal formulations composed of phosphatidylcholine (PC), cholesterol, and α-tocopherol (vit E) were prepared by the thin-film hydration technique. Formulations were characterized in terms of liposome size, pH, surface tension, osmolarity, and viscosity. In vitro tolerance assays were performed on macrophage, human corneal, and conjunctival cell lines at short- and long-term exposures. In vivo ocular tolerance was studied after instillation of the formulation.


RESULTS
The mean liposome size was less than 1 μm and surface tension < 30 mN/m for all formulations. The final liposomal formulation (PC-cholesterol-vit E in a ratio of 8:1:0.8) had physiological values of pH (6.45 ± 0.09), osmolarity (289.43 ± 3.28 mOsm), and viscosity (1.82 ± 0.02 mPa · s). Cell viability was greater than 80% in the corneal and conjunctival cells. This formulation was well tolerated by experimental animals.


CONCLUSIONS
The unpreserved liposomal formulation has suitable properties to be administered by a topical ophthalmic route. The liposome-based artificial tear had good in vitro and in vivo tolerance responses. This formulation, composed of a combination of liposomes and bioadhesive polymers, may be used successfully as a tear film substitute in DE therapy.
Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Complutense University of Madrid, Madrid, Spain Pharmaceutical Innovation in Ophthalmology Research Group, Sanitary Research Institute of the San Carlos Clinical Hospital (IdISSC) and the Ocular Pathology National Net (OFTARED) of the Institute of Health Carlos III, Madrid, Spain.
Marta
M
Vicario-de-la-Torre
Pharmaceutical Innovation in Ophthalmology Research Group, Sanitary Research Institute of the San Carlos Clinical Hospital (IdISSC) and the Ocular Pathology National Net (OFTARED) of the Institute of Health Carlos III, Madrid, Spain Ocular Surface and Inflammation, Ophthalmology Department, San Carlos Clinical Hospital, Madrid, Spain.
José Manuel
JM
Benítez-del-Castillo
Ocular Surface and Inflammation, Ophthalmology Department, San Carlos Clinical Hospital, Madrid, Spain.
Eva
E
Vico
Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Alcalá de Henares, Alcalá de Henares, Madrid, Spain.
Manuel
M
Guzmán
Department of Pharmacology, Faculty of Pharmacy, Complutense University, Madrid, Spain.
Beatriz
B
de-Las-Heras
Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Complutense University of Madrid, Madrid, Spain Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Complutense University of Madrid, Madrid, Spain.
Rocío
R
Herrero-Vanrell
Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Complutense University of Madrid, Madrid, Spain Pharmaceutical Innovation in Ophthalmology Research Group, Sanitary Research Institute of the San Carlos Clinical Hospital (IdISSC) and the Ocular Pathology National Net (OFTARED) of the Institute of Health Carlos III, Madrid, Spain.
Irene T
IT
Molina-Martínez
D000287:Administration, Topical; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000633:toxicity; D002478:Cells, Cultured; D002784:Cholesterol / Q000008:administration & dosage / Q000633:toxicity; D003228:Conjunctiva / Q000166:cytology; D003315:Cornea / Q000166:cytology; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000188:drug therapy*; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage* / Q000009:adverse effects / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D010713:Phosphatidylcholines / Q000008:administration & dosage / Q000633:toxicity; D011817:Rabbits; D014783:Viscosity; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000633:toxicity
D000975:Antioxidants; D008081:Liposomes; D010713:Phosphatidylcholines; D002784:Cholesterol; D024502:alpha-Tocopherol
dry eye; liposomes; nanotechnology