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. Local administration of biodegradable microspheres offers an excellent alternative to multiple administrations, as they are able to deliver the therapeutic molecule in a controlled fashion. Furthermore, injection of microparticles is performed without the need for surgical procedures. As most of the retinal diseases are multifactorial, microspheres result especially promising because they can be loaded with more than one active substance and complemented with the inclusion of additives with pharmacological properties. Personalized therapy can be easily achieved by changing the amount of administered microspheres. Contrary to non-biodegradable devices, biodegradable PLA and PLGA microspheres disappear from the site of administration after delivering the drug. Furthermore, microspheres prepared from these mentioned biomaterials are well tolerated after periocular and intravitreal injections in animals and humans. After injection, PLA and PLGA microspheres suffer aggregation behaving like an implant. Biodegradable microspheres are potential tools in regenerative medicine for retinal repair. According to the reported results, presumably a variety of microparticulate formulations for different ophthalmic therapeutic uses will be available in the clinical practice in the near future.

No abstract

Introduction: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. Areas covered: Knowledge of the different physiological and anatomical structures of the eye, and specially the ocular surface are critical to better understanding and comprehending the characteristics required for the development of topical ophthalmic liposomal formulations. In this review, several features of liposomes are discussed such as the essential materials used for their fabrication, basic structure and preparation methods, from already established to novel techniques, allowing the control and design of special characteristics. Besides, physicochemical properties, purification processes and important strategies to overcome delivery or encapsulation challenges are also presented. Expert opinion: Regarding ocular drug delivery of liposomes, there are some features that can be re-designed. Specific biocompatible and biodegradable materials presenting therapeutic properties, such as lipidic compounds or polymers significantly change the way of tackling ophthalmic diseases. Besides, liposomes entail an effective, safe and versatile strategy for the treatment of diseases in the clinical practice.

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). The use of anti-VEGFs for modifying wound healing in glaucoma filtration surgery (GFS) is also reviewed. Selected studies investigating the use of anti-VEGF agents or antimetabolites in GFS or the management of NVG have demonstrated that these agents can improve surgical outcomes. However, anti-VEGF agents have yet to demonstrate specific advantages over the more established agents commonly used today. Further studies are needed to evaluate the duration of action, dosing intervals, and toxicity profile of these treatments.

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. The present review first outlines our current understanding on the functional anatomy of SC. It then summarizes existing research on SC cell properties; first in the context of their role in glaucoma development/progression and then as a target of novel and emerging antiglaucoma therapies. Evidence from ongoing research efforts to develop effective antiglaucoma therapies targeting SC suggests that this could become a promising site of future therapeutic interventions.

Ocular drug delivery is one of the most challenging fields of pharmaceutical research. They are generally employed to overcome the static (different layers of cornea, sclera, and retina including blood aqueous and blood-retinal barriers) and dynamic barriers (choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution) of the eye. Ophthalmic formulations must be sterile, and the biomaterials used in the preparation of pharmaceutical systems completely compatible and extremely well tolerated by ocular tissues. The location of the target tissue in the eye will determine the route of administration. Ophthalmic administration systems are intended for topical, intraocular and periocular administration. In this review we describe the main pharmaceutical nano-and microsystems currently under study to administrate drugs in the eye, covering microparticles, nanoparticles, liposomes, microemulsions, niosomes and dendrimers. We have performed the corresponding revision of the published scientific literature always emphasizing the technological aspects. The review discusses also the biomaterials used in the preparation of the nano and microsystems of ophthalmic drug delivery, fabrication techniques, therapeutic significances, and future possibilities in the field.

The purpose of this research was to determine the potential use of water-soluble anionic and cationic carbosilane dendrimers (generations 1-3) as mucoadhesive polymers in eyedrop formulations. Cationic carbosilane dendrimers decorated with ammonium -NH3(+) groups were prepared by hydrosylilation of Boc-protected allylamine and followed by deprotection with HCl. Anionic carbosilane dendrimers with terminal carboxylate groups were also employed in this study. In vitro and in vivo tolerance studies were performed in human ocular epithelial cell lines and rabbit eyes respectively. The interaction of dendrimers with transmembrane ocular mucins was evaluated with a surface biosensor. As proof of concept, the hypotensive effect of a carbosilane dendrimer eyedrop formulation containing acetazolamide (ACZ), a poorly water-soluble drug with limited ocular penetration, was tested after instillation in normotensive rabbits. The methodology used to synthesize cationic dendrimers avoids the difficulty of obtaining neutral -NH2 dendrimers that require harsher reaction conditions and also present high aggregation tendency. Tolerance studies demonstrated that both prototypes of water-soluble anionic and cationic carbosilane dendrimers were well tolerated in a range of concentrations between 5 and 10 μM. Permanent interactions between cationic carbosilane dendrimers and ocular mucins were observed using biosensor assays, predominantly for the generation-three (G3) dendrimer. An eyedrop formulation containing G3 cationic carbosilane dendrimers (5 μM) and ACZ (0.07%) (289.4 mOsm; 5.6 pH; 41.7 mN/m) induced a rapid (onset time 1 h) and extended (up to 7 h) hypotensive effect, and led to a significant increment in the efficacy determined by AUC0(8h) and maximal intraocular pressure reduction. This work takes advantage of the high-affinity interaction between cationic carbosilane dendrimers and ocular transmembrane mucins, as well as the tensioactive behavior observed for these polymers. Our results indicate that low amounts of cationic carbosilane dendrimers are well tolerated and able to improve the hypotensive effect of an acetazolamide solution. Our results suggest that carbosilane dendrimers can be used in a safe range of concentrations to enhance the bioavailability of drugs topically administered in the eye.

The results demonstrated that new unpreserved formulations of TM with bioadhesive polymers decreased IOP in rabbits and reached values closer to those reached by traditional solutions. Furthermore, new formulations presented a significantly higher in vitro tolerance than the same compound in traditional formulations. Although unpreserved formulations are usually more expensive, preservative-free antiglaucoma eye drops should improve compliance and adherence in the medical treatment of glaucoma. Bioadhesive polymers could be part of antiglaucoma formulations to reduce ocular toxicity, improve drug efficacy, and protect the ocular surface in long-term therapies.