Nanomedicine for glaucoma: liposomes provide sustained release of latanoprost in the eye

Abstract

Purpose: To report the development and therapeutic evaluation of a liposomal nanocarrier for sustained release of latanoprost, in the rabbit eye. Methods: We fabricated latanoprost-loaded egg-phosphatidylcholine (EggPC) liposomes using the film hydration technique. The delivery vehicles were nano-sized (Z avg = 109 ± 18 nm), had a narrow poly dispersity index (PDI = 0.19 ± 0.04), and a very high loading efficiency (94% ± 5%). Based on in vitro data, we evaluated this formulation for lowering intraocular pressure (IOP) in rabbit eyes. Following a single subconjunctival injection of the latanoprost loaded formulation, the eyes were clinically monitored and the IOP recorded. Results: Latanoprost-loaded EggPC liposomes demonstrated a high drug/lipid mole ratio of 0.181, remained stable for at least 6 months on storage (4°C), and at least 1 month at 25°C. A slow and sustained release of 60% of latanoprost was achieved by 14 days in the in vitro release study. The same formulation demonstrated a greater sustained IOP lowering effect compared with daily administration of topical latanoprost beyond 90 days (4.8 ± 1.5 vs 2.5 ± 0.9 mmHg; P < 0.001). No signs of inflammation were evident in the eyes from slit-lamp examination analysis. Conclusion: The loading required for a long-term sustained delivery of latanoprost for up to 90 days in the rabbit eyes was achieved with EggPC liposomes. A single injection of latanoprost-loaded EggPC liposomes can lower the IOP for up to 90 days, with a greater IOP lowering effect than daily topical administration of latanoprost.

Acceptance, Attitudes, and Beliefs of Singaporean Chinese Toward an Ocular Implant for Glaucoma Drug Delivery

“…Subconjunctival implantation is promising because it has been shown to be safe and efficacious in animal trials, 17,18 and may revolutionize the chronic problem of poor patient adherence. Patient acceptance, therefore, is a crucial component for its implementation.…”

“…9 There is increasing global recognition of the challenges faced in optimal drug delivery for glaucoma management. A review of the current literature revealed various novel drug delivery systems being developed, including liposomes [10][11][12] and nanocapsules, 13 molecularly imprinted contact lenses, 14 microelectrochemical system (MEMS) drug pumps, 15 and subconjunctival injectable implants. 16 All of these aim to improve therapeutic efficiency of drugs delivered to the eye and reduce reliance on patient compliance.…”

“…Specific to subconjunctival implants for sustained drug release, Natarajan et al recently developed a formulation of latanoprost-loaded egg-phosphatidylcholine liposomes for injection into rabbit eyes, 17 and showed that a single injection had an IOP-lowering effect comparable to daily eye drop administration without toxicity or inflammation up to 50 days. 18 To our knowledge, there has yet to be any published trials reporting therapeutic efficiency of such delivery systems in humans.…”

Liposomes as a Novel Ocular Delivery System for Brinzolamide: In Vitro and In Vivo Studies

“…Data are expressed as mean±SD for n=5 lower in Brz-LPs group at any time point from 2 to 10 h than Brz-Sus group (p<0.05). The higher ocular hypotensive effect produced by Brz-LPs attributed to the fact that liposomes had a higher binding affinity to the corneal surface than Brz-Sus (27), which caused better absorption of Brz. The pharmacokinetic study of Brz-LPs is in progress to further explain the mechanism of lowering IOP.…”

Controlled drug delivery for glaucoma therapy using montmorillonite/Eudragit microspheres as an ion-exchange carrier

“…1 It is commonly considered as the second leading cause of blindness and about 60.5 million individuals have been affected worldwide. 2 High intraocular pressure (IOP) is the main risk factor, which leads to the degeneration of axons from the retinal ganglion cells. Therefore, many kinds of IOP lowering medications are used to manage the disease symptoms, such as timolol, betaxolol, epinephrine, pilocarpine, and dorzolamide.…”