RESUMEN
The first line of glaucoma treatment focuses on reducing intraocular pressure (IOP) through the prescription of topical prostaglandin analogues, such as latanoprost (LAT). Topical ophthalmic medicines have low bioavailability due to their rapid elimination from the ocular surface. Nanotechnology offers innovative ways of enhancing the ocular bioavailability of antiglaucoma agents while reducing administration frequency. This study aims to combine LAT-loaded synthetic phosphatidylcholine liposomes with hyaluronic acid (0.2% w/v) and the osmoprotectants betaine (0.40% w/v) and leucine (0.90% w/v) (LAT-HA-LIP) to extend the hypotensive effect of LAT while protecting the ocular surface. LAT-HA-LIP was prepared as a mixture of 1,2-dioleoyl-sn-glycero-3-phosphocholine and 1,2-dimyristoyl-sn-glycero-3-phosphocholine, cholesterol and α-tocopherol acetate. LAT-HA-LIP exhibited high drug-loading capacity (104.52 ± 4.10%), unimodal vesicle sizes (195.14 ± 14.34 nm) and a zeta potential of -13.96 ± 0.78 mV. LAT-HA-LIP was isotonic (284.00 ± 1.41 mOsm L-1), had neutral pH (7.63 ± 0.01) and had suitable surface tension (44.07 ± 2.70 mN m-1) and viscosity (2.69 ± 0.15 mPa s-1) for topical ophthalmic administration. LAT-HA-LIP exhibited optimal in vitro tolerance in human corneal and conjunctival epithelial cells. No signs of ocular alteration or discomfort were observed when LAT-HA-LIP was instilled in albino male New Zealand rabbits. Hypotensive studies revealed that, after a single eye drop, the effect of LAT-HA-LIP lasted 24 h longer than that of a marketed formulation and that relative ocular bioavailability was almost three times higher (p < 0.001). These findings indicate the potential ocular protection and hypotensive effect LAT-HA-LIP offers in glaucoma treatment.
Asunto(s)
Antihipertensivos , Ácido Hialurónico , Latanoprost , Liposomas , Fosfatidilcolinas , Latanoprost/administración & dosificación , Latanoprost/química , Ácido Hialurónico/química , Ácido Hialurónico/administración & dosificación , Fosfatidilcolinas/química , Fosfatidilcolinas/administración & dosificación , Humanos , Animales , Antihipertensivos/administración & dosificación , Antihipertensivos/química , Antihipertensivos/farmacocinética , Antihipertensivos/farmacología , Presión Intraocular/efectos de los fármacos , Conejos , Masculino , Línea CelularRESUMEN
Given that nonadherence is related to subject characteristics and drug tolerance and preserved eye drops tend to be more intolerable than preservative-free ones, we conducted a phase 4, parallel-grouped, investigator-blind, active-control, randomized, multicenter study. A total of 51 patients with intraocular pressure (IOP) ≥ 15 mmHg diagnosed with open-angle glaucoma or ocular hypertension were randomly assigned to the preserved latanoprost group (n = 26) and the preservative-free latanoprost group (n = 25). The efficacy variables were corneal/conjunctival staining grade, Ocular Surface Disease Index (OSDI), adherence at 12 weeks after the first administration; corneal/conjunctival staining grade at 4 weeks; and IOP, tear break-up time (TBUT), and hyperemia score at 4 and 12 weeks. The safety variables included visual acuity and drug tolerance questionnaire results. There was no statistically significant difference in corneal/conjunctival staining grade, OSDI, or TBUT between the groups at 4 and 12 weeks. However, the adherence rate was higher and the hyperemia score was lower in the preservative-free group than in the preserved group. The severity and duration of stinging/burning sensation were lower in the preservative-free group than in the preserved group. Overall, preservative-free latanoprost showed better ocular tolerance assessed by hyperemia scores and stinging/burning symptoms following higher adherence than preserved latanoprost.
Asunto(s)
Glaucoma de Ángulo Abierto/tratamiento farmacológico , Latanoprost/administración & dosificación , Hipertensión Ocular/tratamiento farmacológico , Soluciones Oftálmicas/administración & dosificación , Anciano , Esquema de Medicación , Femenino , Humanos , Análisis de Intención de Tratar , Latanoprost/química , Latanoprost/farmacología , Masculino , Persona de Mediana Edad , Soluciones Oftálmicas/química , Soluciones Oftálmicas/farmacología , Conservadores Farmacéuticos/química , Cumplimiento y Adherencia al Tratamiento , Resultado del TratamientoRESUMEN
Objective: Glaucoma is a leading cause of irreversible blindness worldwide. Whereas latanoprost is one of the most effective drugs in glaucoma treatment, its eye drops need frequent application leading to lack of patient adherence. This study aimed to develop a patient-friendly niosome-in-gel system for the sustained ocular delivery of latanoprost.Methods: Niosomes were prepared by the reverse-phase evaporation technique and optimized for different formulation parameters, such as cholesterol/surfactant and drug/surfactant ratios. Selected niosomal formulations were incorporated into different gels and their viscosity and drug release kinetics were evaluated. Optimal niosomal gel was evaluated in vivo in rabbits' eyes for irritation potential and ability to reduce intraocular pressure.Results: FT-IR studies showed that there were nonspecific interactions between latanoprost and different niosomal components leading to drug encapsulation efficiency ≥88%. Latanoprost encapsulation efficiency increased with the drug/surfactant ratio and encapsulation efficiency â¼98% was obtained at a ratio of 50%. Pluronic® F127 had the best ability to sustain drug release from the niosomes. In rabbits' eyes, this gel was free of toxic and irritant effects and reduced intraocular pressure over a period of three days, which was significantly longer than that of commercial latanoprost eye drops.Conclusion: Latanoprost niosomal Pluronic® F127 gel may find applications in glaucoma management.
Asunto(s)
Preparaciones de Acción Retardada/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Glaucoma/tratamiento farmacológico , Latanoprost/administración & dosificación , Absorción Ocular/efectos de los fármacos , Soluciones Oftálmicas/administración & dosificación , Administración Oftálmica , Animales , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/metabolismo , Glaucoma/metabolismo , Glaucoma/patología , Latanoprost/química , Latanoprost/metabolismo , Liposomas , Masculino , Absorción Ocular/fisiología , Soluciones Oftálmicas/química , Soluciones Oftálmicas/metabolismo , RatasRESUMEN
This study investigated the potential of delivering an anti-glaucoma drug using commercial silicone hydrogel (SiHy) contact lenses. The moderately hydrophobic drug latanoprost was rapidly loaded in 4 min by swelling contact lenses in a solution of the drug in n-propanol. A fraction of the drug was radiolabeled, thus allowing measurement of the uptake and subsequent release of drug into artificial tear fluid. Three questions were addressed: (1) how much drug can be loaded into each type of lens, (2) how fast is drug release, and (3) how are these values related to the contact lens chemistry. The results showed that much more latanoprost could be loaded into SiHy lenses than a conventional contact lens of poly(hydroxyethyl methacrylate). The drug uptake correlated with the amount of swelling in n-propanol, with Galyfilcon lenses having the greatest swelling and highest drug uptake. The drug release from the SiHy lenses occurred over days, whereas the conventional lens released nearly all drug in a burst over a few hours. To examine correlations between lens chemistry, drug chemistry and uptake, and solvent chemistry, the Hansen solubility parameters were calculated using estimates of contact lens chemistry. These results showed that drug uptake in SiHy lenses correlated with favorable solubility parameter interactions between the n-propanol and the lens material, but did not correlate with interactions between the drug and the lens materials.