title: Hybrid formulations of liposomes and bioadhesive polymers improve the hypotensive effect of the melatonin analogue 5-MCA-NAT in rabbit eyes.
abstract: For the treatment of chronic ocular diseases such as glaucoma, continuous instillations of eye drops are needed. However, frequent administrations of hypotensive topical formulations can produce adverse ocular surface effects due to the active substance or other components of the formulation, such as preservatives or other excipients. Thus the development of unpreserved formulations that are well tolerated after frequent instillations is an important challenge to improve ophthalmic chronic topical therapies. Furthermore, several components can improve the properties of the formulation in terms of efficacy. In order to achieve the mentioned objectives, we have developed formulations of liposomes (150-200 nm) containing components similar to those in the tear film and loaded with the hypotensive melatonin analog 5-methoxycarbonylamino-N-acetyltryptamine (5-MCA-NAT, 100 µM). These formulations were combined with mucoadhesive (sodium hyaluronate or carboxymethylcellulose) or amphiphilic block thermosensitive (poloxamer) polymers to prolong the hypotensive efficacy of the drug. In rabbit eyes, the decrease of intraocular pressure with 5-MCA-NAT-loaded liposomes that were dispersed with 0.2% sodium hyaluronate, 39.1±2.2%, was remarkably higher compared to other liposomes formulated without or with other bioadhesive polymers, and the effect lasted more than 8 hours. According to the results obtained in the present work, these technological strategies could provide an improved modality for delivering therapeutic agents in patients with glaucoma.
authors.affiliation: Department of Pharmacy, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, CONICET, Edificio de Ciencias II, Ciudad Universitaria, Córdoba, Argentina.
authors.forename: Daniela
authors.initials: D
authors.lastname: Quinteros
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Complutense University of Madrid, 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.
authors.forename: Marta
authors.initials: M
authors.lastname: Vicario-de-la-Torre
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Complutense University of Madrid, 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.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Andrés-Guerrero
authors.affiliation: Department of Pharmacy, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, CONICET, Edificio de Ciencias II, Ciudad Universitaria, Córdoba, Argentina.
authors.forename: Santiago
authors.initials: S
authors.lastname: Palma
authors.affiliation: Department of Pharmacy, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, CONICET, Edificio de Ciencias II, Ciudad Universitaria, Córdoba, Argentina.
authors.forename: Daniel
authors.initials: D
authors.lastname: Allemandi
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Complutense University of Madrid, 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.
authors.forename: Rocío
authors.initials: R
authors.lastname: Herrero-Vanrell
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Complutense University of Madrid, 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.
authors.forename: Irene T
authors.initials: IT
authors.lastname: Molina-Martínez
mesh_terms: D000269:Adhesives / Q000737:chemistry*; D000818:Animals; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D065546:Drug Liberation; D006863:Hydrogen-Ion Concentration; D007429:Intraocular Pressure / Q000187:drug effects; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D008550:Melatonin / Q000031:analogs & derivatives*; D009994:Osmolar Concentration; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D011817:Rabbits; D013666:Tears / Q000737:chemistry / Q000187:drug effects; D014363:Tryptamines / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology*; D014783:Viscosity
chemical_list: C413586:5-methoxycarbonylamino-N-acetyltryptamine; D000269:Adhesives; D000959:Antihypertensive Agents; D008081:Liposomes; D011108:Polymers; D014363:Tryptamines; D008550:Melatonin