The treatment of the posterior-segment ocular diseases, such as age-related eye diseases (AMD) or diabetic retinopathy (DR), present a challenge for ophthalmologists due to the complex anatomy and physiology of the eye. This specialized organ is composed of various static and dynamic barriers that restrict drug delivery into the target site of action. Despite numerous efforts, effective intraocular drug delivery remains unresolved and, therefore, it is highly desirable to improve the current treatments of diseases affecting the posterior cavity. This review article gives an overview of pharmacokinetic and biopharmaceutics aspects for the most commonly-used ocular administration routes (intravitreal, topical, systemic, and periocular), including information of the absorption, distribution, and elimination, as well as the benefits and limitations of each one. This article also encompasses different conventional and novel drug delivery systems designed and developed to improve drug pharmacokinetics intended for the posterior ocular segment treatment.

Background: the present work describes the preparation, characterization and optimization of eight types of PLGA-based nanosystems (nanospheres and nanocapsules) as innovative mucoadhesive drug delivery systems of lactoferrin, in order to achieve a preclinical consistent base as an alternative pharmacological treatment to different ocular syndromes and diseases. Methods: All different nanoparticles were prepared via two modified nanoprecipitation techniques, using a three-component mixture of drug/polymer/surfactant (Lf/PLGA/Poloxamer), as a way to overcome the inherent limitations of conventional PLGA NPs. These modified polymeric nanocarriers, intended for topical ophthalmic administration, were subjected to in vitro characterization, surface modification and in vitro and in vivo assessments. Results: An appropriate size range, uniform size distribution and negative ζ potential values were obtained for all types of formulations. Lactoferrin could be effectively included into all types of nanoparticles with appropriate encapsulation efficiency and loading capacity values. A greater, extended, and controlled delivery of Lf from the polymeric matrix was observed through the in vitro release studies. No instability or cytotoxicity was proved for all the formulations by means of organotypic models. Additionally, mucoadhesive in vitro and in vivo experiments show a significant increase in the residence time of the nanoparticles in the eye surface. Conclusions: all types of prepared PLGA nanoparticles might be a potential alternative for the topical ophthalmic administration of lactoferrin.

Uveitis is a vision inflammatory disorder with a high prevalence in developing countries. Currently, marketed treatments remain limited and reformulation is usually performed to obtain a tacrolimus eye drop as a therapeutic alternative in corticosteroid-refractory eye disease. The aim of this work was to develop a mucoadhesive, non-toxic and stable topical ophthalmic formulation that can be safely prepared in hospital pharmacy departments. Four different ophthalmic formulations were prepared based on the tacrolimus/hydroxypropyl-β-cyclodextrin (HPβCD) inclusion complexes’ formation. Phase solubility diagrams, Nuclear Magnetic Resonance (NMR) and molecular modeling studies showed the formation of 1:1 and 1:2 tacrolimus/HPβCD inclusion complexes, being possible to obtain a 0.02% (w/v) tacrolimus concentration by using 40% (w/v) HPβCD aqueous solutions. Formulations also showed good ophthalmic properties in terms of pH, osmolality and safety. Stability studies proved these formulations to be stable for at least 3 months in refrigeration. Ex vivo bioadhesion and in vivo ocular permanence showed good mucoadhesive properties with higher ocular permanence compared to the reference pharmacy compounding used in clinical settings (t_1/2 of 86.2 min for the eyedrop elaborated with 40% (w/v) HPβCD and Liquifilm^® versus 46.3 min for the reference formulation). Thus, these novel eye drops present high potential as a safe alternative for uveitis treatment, as well as a versatile composition to include new drugs intended for topical ophthalmic administration.

Fungal keratitis (FK) is a corneal mycotic infection that can lead to vision loss. Furthermore, the severity of FK is aggravated by the emergence of resistant fungal species. There is currently only one FDA-approved formulation for FK treatment forcing hospital pharmacy departments to reformulate intravenous drug preparations with unknown ocular bioavailability and toxicity. In the present study, natamycin/voriconazole formulations were developed and characterized to improve natamycin solubility, permanence, and safety. The solubility of natamycin was studied in the presence of two cyclodextrins: HPβCD and HPγCD. The HPβCD was chosen based on the solubility results. Natamycin/cyclodextrin (HPβCD) inclusion complexes characterization and a competition study between natamycin and voriconazole were conducted by NMR (Nuclear Magnetic Resonance). Based on these results, several eye drops with different polymer compositions were developed and subsequently characterized. Permeability studies suggested that the formulations improved the passage of natamycin through the cornea compared to the commercial formulation Natacyn^®. The ocular safety of the formulations was determined by BCOP and HET-CAM. The antifungal activity assay demonstrated the ability of our formulations to inhibit the in vitro growth of different fungal species. All these results concluded that the formulations developed in the present study could significantly improve the treatment of FK.

The treatment of posterior segment ocular diseases, such as age-related macular degeneration and diabetic retinopathy, poses a significant challenge for ophthalmologists due to the eye's complex anatomy and physiological barriers. To overcome these challenges, intravitreal drug delivery offers a promising solution by enabling direct administration of therapeutic agents into the pathological area through an injection. However, these injections are highly invasive and carry several risks, including infection, retinal detachment, and increased intraocular pressure. As a result, considerable efforts have been directed toward developing drug delivery platforms (implants, nano- and microparticles, and hydrogels) capable of providing sustained drug release over extended periods. These long-acting systems aim to reduce the frequency of injections, thereby improving patient quality of life and decreasing the overall economic burden of treatment. This review provides an overview of intravitreal drug delivery systems, evaluating their clinical applicability and the potential challenges that must be addressed before they can be successfully translated into marketed drug products.

Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are two techniques used in the resection of gastrointestinal mucosal polyps. The aim of this work is the development and evaluation of an innovative polymeric solution containing sodium carboxymethylcellulose and hyaluronic acid. For this purpose, several mixtures of these two main components, as well as other components such as fructose, citric acid, and zinc, are evaluated in terms of physicochemical and microbiological properties, rheological behavior, extensibility, syringeability, and stability at different storage conditions. Furthermore, the potential production of mucosal elevation and duration is also studied by an ex vivo model using porcine stomach and colon. Results show that the developed polymeric solutions possess optimal values of pH, from 4.58 to 6.63, for their use in the gastrointestinal tract. The formulations exhibit both Newtonian and pseudoplastic behaviors with different viscosity values as a function of their composition. All formulations exhibit high stability properties and no bacterial or fungal growth is detected. MCS01 and MCS05 are the polymeric solutions with the best syringeability results. In this line, MCS05 is the formulation that provides the highest, 2.20 ± 0.18 cm and 1.40 ± 0.11 cm, and longest-lasting, for more than 120 min, elevation effect on porcine submucosal stomach and colon tissues, respectively. Thus, it can be concluded that polymeric solution MCS05 might be considered as a promising tool for use in human EMR and ESD.