Enhancing the hypotensive effect of latanoprost by combining synthetic phosphatidylcholine liposomes with hyaluronic acid and osmoprotective agents.

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.

Smart biodegradable hydrogels: Drug-delivery platforms for treatment of chronic ophthalmic diseases affecting the back of the eye.

This paper aims to develop smart hydrogels based on functionalized hyaluronic acid (HA) and PLGA-PEG-PLGA (PLGA,poly-(DL-lactic-co-glycolic acid); PEG,polyethylene glycol) for use as intraocular drug-delivery platforms. Anti-inflammatory agent dexamethasone-phosphate (0.2 %w/v) was the drug selected to load on the hydrogels.

Novel Osmoprotective DOPC-DMPC Liposomes Loaded with Antihypertensive Drugs as Potential Strategy for Glaucoma Treatment.

Glaucoma is a group of chronic irreversible neuropathies that affect the retina and the optic nerve. It is considered one of the leading causes of blindness in the world. Although it can be due to various causes, the most important modifiable risk factor is the elevated intraocular pressure (IOP).

A novel osmoprotective liposomal formulation from synthetic phospholipids to reduce hyperosmolar stress in dry eye treatments.

Dry eye disease (DED) is a worldwide, multifactorial disease mainly caused by a deficit in tear production or increased tear evaporation with an increase in tear osmolarity and inflammation. This causes discomfort and there is a therapeutic need to restore the homeostasis of the ocular surface. The aim of the present work was to develop a biodegradable and biocompatible liposomal formulation from the synthetic phospholipids 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) that is able to reduce the effects of hypertonic stress by helping to restore the lipid layer of the tear film.

Validation of a Rapid and Easy-to-Apply Method to Simultaneously Quantify Co-Loaded Dexamethasone and Melatonin PLGA Microspheres by HPLC-UV: Encapsulation Efficiency and In Vitro Release.

This paper discusses the development and validation of a rapid method for the reversed phase HPLC-UV quantification of biodegradable poly(D,L-lactic-co-glycolic) acid (PLGA) microspheres co-loaded with two neuroprotective agents (dexamethasone and melatonin) (DX-MEL-MSs) to be intravitreally administered as a promising glaucoma treatment. The study was performed to validate two procedures that quantify the content of the two active substances entrapped into the polymer matrix during an encapsulation efficiency assay and the amount of drugs liberated over time during the in vitro release assay. The reversed-phase method allowed for the simultaneous determination of dexamethasone and melatonin, which were respectively detected at 240.

Cytokine profile in tear and aqueous humor of primary open-angle patients as a prognostic factor for trabeculectomy outcome.

Objective: To evaluate the cytokine profile in tear and aqueous humor in primary open-angle glaucoma before trabeculectomy and correlate preoperative cytokine levels with the surgical outcome.

Methods: Prospective study. Twenty-nine patients with primary open-angle glaucoma undergoing primary trabeculectomy were included.

Posterior Segment Ophthalmic Drug Delivery: Role of Muco-Adhesion with a Special Focus on Chitosan.

Posterior segment eye diseases (PSEDs) including age macular degeneration (AMD) and diabetic retinopathy (DR) are amongst the major causes of irreversible blindness worldwide. Due to the numerous barriers encountered, highly invasive intravitreal (IVT) injections represent the primary route to deliver drugs to the posterior eye tissues. Thus, the potential of a more patient friendly topical route has been widely investigated.

Proinflammatory Cytokine Profile Differences between Primary Open-Angle and Pseudoexfoliative Glaucoma.

Introduction: Few studies have investigated glaucoma biomarkers in aqueous humor and tear and have found elevations of proinflammatory cytokines in patients with primary open-angle glaucoma (POAG) and pseudoexfoliative glaucoma (PXG). In this study, we investigate differences in inflammatory cytokines between POAG and PXG patients to find specific disease biomarkers.

Methods: For this purpose, tear and aqueous humor samples of 14 eyes with POAG and 15 eyes with PXG undergoing cataract surgery were immunoassayed for 27 proinflammatory cytokines.

The Effect of a Triple Combination of Bevacizumab, Sodium Hyaluronate and a Collagen Matrix Implant in a Trabeculectomy Animal Model.

Currently available anti-scarring treatments for glaucoma filtration surgery (GFS) have potentially blinding complications, so there is a need for alternative and safer agents. The effects of the intrableb administration of a new combination of the anti-VEGF bevacizumab, sodium hyaluronate and a collagen matrix implant were investigated in a rabbit model of GFS, with the purpose of modulating inflammation, angiogenesis, fibroblast migration and fibrogenesis in the wound healing process. A comparative-effectiveness study was performed with twenty-four rabbits, randomly assigned to the following treatments: (a) biodegradable collagen matrix implant (Olo), (b) bevacizumab-loaded collagen matrix implant (Olo-BVZ), (c) bevacizumab-loaded collagen matrix implant combined with sodium hyaluronate (Olo-BVZ-H5) and (d) sham-operated animals (control).

Thermo-Responsive PLGA-PEG-PLGA Hydrogels as Novel Injectable Platforms for Neuroprotective Combined Therapies in the Treatment of Retinal Degenerative Diseases.

The present study aims to develop a thermo-responsive-injectable hydrogel (HyG) based on PLGA-PEG-PLGA (PLGA = poly-(DL-lactic acid co-glycolic acid); PEG = polyethylene glycol) to deliver neuroprotective agents to the retina over time. Two PLGA-PEG PLGA copolymers with different PEG:LA:GA ratios (1:1.54:23.

Dexamethasone PLGA Microspheres for Sub-Tenon Administration: Influence of Sterilization and Tolerance Studies.

Many diseases affecting the posterior segment of the eye require repeated intravitreal injections with corticosteroids in chronic treatments. The periocular administration is a less invasive route attracting considerable attention for long-term therapies. In the present work, dexamethasone-loaded poly(lactic--glycolic) acid (PLGA) microspheres (Dx-MS) were prepared using the oil-in-water (O/W) emulsion solvent evaporation technique.

Liposomes as vehicles for topical ophthalmic drug delivery and ocular surface protection.

The development of ophthalmic formulations able to deliver hydrophilic and hydrophobic drugs to the inner structures of the eye and restore the preocular tear film has been a leading topic of discussion over the last few years. In this sense, liposomes represent a suitable strategy to achieve these objectives in ocular drug delivery. Knowledge of the different physiological and anatomical eye structures, and specially the ocular surface are critical to better understanding and comprehending the characteristics required for the development of topical ophthalmic liposomal formulations.

Gelatin Nanoparticles-HPMC Hybrid System for Effective Ocular Topical Administration of Antihypertensive Agents.

The increment in ocular drug bioavailability after topical administration is one of the main challenges in pharmaceutical technology. For several years, different strategies based on nanotechnology, hydrogels or implants have been evaluated. Nowadays, the tolerance of ophthalmic preparations has become a critical issue and it is essential to the use of well tolerated excipients.

Trojan Microparticles Potential for Ophthalmic Drug Delivery.

The administration of drugs to treat ocular disorders still remains a technological challenge in this XXI century. Although there is an important arsenal of active molecules useful to treat ocular diseases, ranging from classical compounds to biotechnological products, currenty, no ideal delivery system is able to profit all their therapeutic potential. Among the Intraocular Drug Delivery Systems (IODDS) proposed to overcome some of the most important limitations, microsystems and nanosystems have raised high attention.

Amphiphilic Acrylic Nanoparticles Containing the Poloxamer Star Bayfit® 10WF15 as Ophthalmic Drug Carriers.

Topical application of drops containing ocular drugs is the preferred non-invasive route to treat diseases that affect the anterior segment of the eye. However, the formulation of eye drops is a major challenge for pharmacists since the access of drugs to ocular tissues is restricted by several barriers. Acetazolamide (ACZ) is a carbonic anhydrase inhibitor used orally for the treatment of ocular hypertension in glaucoma.

Microspheres as intraocular therapeutic tools in chronic diseases of the optic nerve and retina.

Pathologies affecting the optic nerve and the retina are one of the major causes of blindness. These diseases include age-related macular degeneration (AMD), diabetic retinopathy (DR) and glaucoma, among others. Also, there are genetic disorders that affect the retina causing visual impairment.

Targeting Schlemm's Canal in the Medical Therapy of Glaucoma: Current and Future Considerations.

Schlemm's canal (SC) is a unique, complex vascular structure responsible for maintaining fluid homeostasis within the anterior segment of the eye by draining the excess of aqueous humour. In glaucoma, a heterogeneous group of eye disorders afflicting approximately 60 million individuals worldwide, the normal outflow of aqueous humour into SC is progressively hindered, leading to a gradual increase in outflow resistance, which gradually results in elevated intraocular pressure (IOP). By and large available antiglaucoma therapies do not target the site of the pathology (SC), but rather aim to decrease IOP by other mechanisms, either reducing aqueous production or by diverting aqueous flow through the unconventional outflow system.

Evaluation of polyesteramide (PEA) and polyester (PLGA) microspheres as intravitreal drug delivery systems in albino rats.

Purpose: To study the suitability of injectable microspheres based on poly(ester amide) (PEA) or poly lactic-co-glycolic acid (PLGA) as potential vehicles for intravitreal drug delivery in rat eyes. Dexamethasone-loaded PEA microspheres (PEA + DEX) were also evaluated.

Methods: Forty male Sprague Dawley rats were divided into four groups that received different intravitreally injected microspheres: PEA group (n = 12); PLGA group (n = 12); PEA + DEX group (n = 8); and control group (no injection, n = 8).

Current Perspectives on the Use of Anti-VEGF Drugs as Adjuvant Therapy in Glaucoma.

The approval of one of the first anti-vascular endothelial growth factor (VEGF) agents for the treatment of neovascular age-related macular degeneration one decade ago marked the beginning of a new era in the management of several sight-threatening retinal diseases. Since then, emerging evidence has demonstrated the utility of these therapies for the treatment of other ocular conditions characterized by elevated VEGF levels. In this article we review current perspectives on the use of anti-VEGF drugs as adjuvant therapy in the management of neovascular glaucoma (NVG).

Novel biodegradable polyesteramide microspheres for controlled drug delivery in Ophthalmology.

Most of the posterior segment diseases are chronic and multifactorial and require long-term intraocular medication. Conventional treatments of these pathologies consist of successive intraocular injections, which are associated with adverse effects. Successful therapy requires the development of new drug delivery systems able to release the active substance for a long term with a single administration.

Block copolypeptide nanoparticles for the delivery of ocular therapeutics.

Self-assembling block copolypeptides were prepared by sequential ring-opening polymerization of N-carboxyanhydride (NCA) derivatives of γ-benzyl-L-glutamic acid and ε-carbobenzyloxy-L-lysine, followed by selective deprotection of the benzyl glutamate block. The synthesized polymers had number average molecular weights close to theoretical values, and had low dispersities (ĐM  = 1.15-1.

Hybrid formulations of liposomes and bioadhesive polymers improve the hypotensive effect of the melatonin analogue 5-MCA-NAT in rabbit eyes.

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.

The potential of using biodegradable microspheres in retinal diseases and other intraocular pathologies.

Pathologies affecting the posterior segment of the eye are one of the major causes of blindness in developed countries and are becoming more prevalent due to the increase in society longevity. Successful therapy of diseases affecting the back of the eye requires effective concentrations of the active substance maintained during a long period of time in the intraocular target site. Treatment of vitreoretinal diseases often include repeated intravitreous injections that are associated with adverse effects.

Comparison of the in vitro tolerance and in vivo efficacy of traditional timolol maleate eye drops versus new formulations with bioadhesive polymers.

Purpose: To assess the in vitro tolerance and in vivo efficacy of new unpreserved formulations of timolol maleate (TM) in aqueous solutions of bioadhesive polymers used for dry eye treatment and to compare them with three traditional TM formulations: unpreserved Timabak (Thea, Madrid, Spain), benzalkonium chloride (BAK)-preserved Timoftol (Frosst Laboratories, Madrid, Spain), and BAK-preserved Timolol Sandoz (Frosst Laboratories).

Methods: New formulations were composed of TM (0.5%) and carboxymethyl cellulose (0.

The use of mucoadhesive polymers to enhance the hypotensive effect of a melatonin analogue, 5-MCA-NAT, in rabbit eyes.

Purpose: 5-Methoxy-carbonylamino-N-acetyltryptamine (5-MCA-NAT, a melatonin receptor agonist) produces a clear intraocular pressure (IOP) reduction in New Zealand White rabbits and glaucomatous monkeys. The goal of this study was to evaluate whether the hypotensive effect of 5-MCA-NAT was enhanced by the presence of cellulose derivatives, some of them with bioadhesive properties, as well as to determine whether these formulations were well tolerated by the ocular surface.

Methods: Formulations were prepared with propylene glycol (0.