Gantrez AN Nanoparticles for Ocular Delivery of Memantine: In vitro Release Evaluation in Albino Rabbits

Abstract

Aim: To prepare and evaluate the in vitro release of memantine-loaded poly(anhydride) (Gantrez®) nanoparticles (NPs). The clinical safety and retinal toxicity caused by unloaded NPs after sub-Tenon and intravitreal ocular injections were also evaluated. Methods: Preparation and characterization of this type of NP as well as the in vitro release study are described. Twenty-three healthy New Zealand rabbits were used for clinical and histological assessment after sub-Tenon and intravitreal ocular injections of unloaded NPs. Results: The amount of drug associated with NPs was 55 µg of memantine/mg of NP. The release profile of memantine from this type of NPs was characterized by an initial burst effect, followed by continuous release of the drug for at least 15 days. No relevant complications were found during the clinical follow-up. The histological evaluation suggested that Gantrez NPs are well tolerated after sub-Tenon ocular injection and that signs of inflammation during the first days after intravitreal ocular injections can be considered a normal reaction of the eye’s defence mechanism.

Memantine‐Loaded PEGylated Biodegradable Nanoparticles for the Treatment of Glaucoma

“…Other groups have previously formulated memantine into nanoparticles. Prieto and colleagues developed Gantrez, a memantine‐loaded poly(anhydride) nanoparticle formulation which possessed a similar diameter as our formulation but only contained 0.055 mg of memantine per mg of nanoparticles . While the authors demonstrated sustained release of memantine from these formulations after subtenon and intravitreal injection in the rabbit, the authors did not investigate topical administration.…”

“…A key challenge for MEM in glaucoma is the development of a safe and effective means of long‐lasting delivery of MEM to the back of the eye . Incorporation of MEM into a nanoparticle drug delivery systems could provide a strategy to enhance the efficacy of this agent by increasing concentrations in target retinal tissues whilst reducing the risk of side effects associated with systemic dosing regimens .…”

“…In this study, we sought to develop a novel biodegradable PLGA‐PEG nanoparticle formulation of MEM which could be applied as an eye drop once a day. Topical administration is favored over subtenon or intravitreal implants owing to noninvasiveness, reduced risk of side effects, ability to self‐administer and inherent socioeconomic costs . Encapsulation of MEM in MEM‐PLGA‐PEG NPs was achieved using a double emulsion method.…”

Towards C1 chemistry: methanol vinylation by CaC2 in water in the presence of potassium or sodium carbonates

“…Among the poly(vinyl ethers), poly(methyl vinyl ether) is a special case because it belongs to the class of thermo‐responsive polymers and exhibits a lower critical solution temperature (LCST) around 36 °C . Copolymers of MVE with maleic anhydride are widely used in medicine and pharmacology, in paper and textile industries, for manufacture of cosmetics and toiletry, as bioadhesives for drug delivery options and components of cellulosic biocomposites . Besides, these copolymers form interpolymer complexes possessing valuable properties …”

Nanotechnology in Corneal Neovascularization Therapy—A Review

“…58 A separate study using polyanhydride nanoparticles to deliver mamantine into the eye showed that nanoparticles sustained drug release for 15 days following an initial burst release. 59 This suggests that drug therapy using these types of nanocarriers allows for extended, continuous release of the drug, which overcomes another obstacle facing conventional treatment options. In another study, 20-nm gold nanoparticles (Au-NPs) were able to pass through the blood-retinal barrier and associate with retinal-epithelial cells, retinoblastoma cells, and astrocytes without any observed toxicity.…”