Nanotherapeutics based on biocompatible lipid matrices allow for enhanced solubility of poorly soluble compounds in the treatment of ophthalmic diseases, overcoming the anatomical and physiological barriers present in the eye, which, despite the ease of access, remains strongly protected. Micro-/nanoemulsions, solid lipid nanoparticles (SLN) or nanostructured lipid carriers (NLC) combine liquid and/or solid lipids with surfactants, improving drug stability and ocular bioavailability. Current research and development approaches based on try-and-error methodologies are unable to easily fine-tune nanoparticle populations in order to overcome the numerous constraints of ocular administration routes, which is believed to hamper easy approval from regulatory agencies for these systems. The predictable quality and specifications of the product can be achieved through quality-by-design (QbD) implementation in both research and industrial environments, in contrast to the current quality-by-testing (QbT) framework. Mathematical modelling of the expected final nanoparticle characteristics by variation of operator-controllable variables of the process can be achieved through adequate statistical design-of-experiments (DoE) application. This multivariate approach allows for optimisation of drug delivery platforms, reducing research costs and time, while maximising the understanding of the production process. This review aims to highlight the latest efforts in implementing the design of experiments to produce optimised lipid-based nanocarriers intended for ophthalmic administration. A useful background and an overview of the different possible approaches are presented, serving as a starting point to introduce the design of experiments in current nanoparticle research.

Corticosteroids, although highly effective for the treatment of both anterior and posterior ocular segment inflammation, still nowadays struggle for effective drug delivery due to their poor solubilization capabilities in water. This research work aims to develop nanostructured lipid carriers (NLC) intended for periocular administration of dexamethasone acetate to the posterior segment of the eye. Pre-formulation studies were initially performed to find solid and liquid lipid mixtures for dexamethasone acetate solubilization. Pseudoternary diagrams at 65 °C were constructed to select the best surfactant based on the macroscopic transparency and microscopic isotropy of the systems. The resulting NLC, obtained following an organic solvent-free methodology, was composed of triacetin, Imwitor® 491 (glycerol monostearate >90%) and tyloxapol with Z-average = 106.9 ± 1.2 nm, PDI = 0.104 ± 0.019 and zeta potential = −6.51 ± 0.575 mV. Ex vivo porcine sclera and choroid permeation studies revealed a considerable metabolism in the sclera of dexamethasone acetate into free dexamethasone, which demonstrated higher permeation capabilities across both tissues. In addition, the NLC behavior once applied onto the sclera was further studied by means of multiphoton microscopy by loading the NLC with the fluorescent probe Nile red.

Purpose: Ex vivo ocular models are a valuable tool for quick screening ophthalmic formulations through permeation and retention studies. We hereby present a 3D‐printed set‐up consisting of a combination of two devices, allowing for the ex vivo study of transscleral drug delivery with fresh whole swine eyes. Methods: The two devices were drafted on a CAD (computer aided design) software and 3D printed with three different printing techniques: selective laser sintering (SLS), fused deposition modelling (FDM) and masked stereolithography (MSLA). The first device was designed to guarantee the contact between drug formulation (liquid or semisolid) and the scleral surface in a defined permeation area for up to 24 h. The second device was then designed to maintain up to three ocular bulbs at constant temperature (37°C) and humidity values. Results: MSLA 3D printing technique was selected due to its versatility, superior print detail and a low unitary cost. In addition, the other two explored techniques delivered relatively porous prints that do not guarantee the required water and air tightness of the devices. The first device was optimized in order to maximize adherence onto the scleral surface and thus anatomically adjusted to porcine scleral curvature. Firm anchorage onto the ocular surface was achieved through a ring‐shaped vacuum chamber easily controlled with a syringe. The second device allowed to immobilize the ocular bulb during the experiment, preserve ocular hydration, and maintain a fixed working temperature by placement into a water bath. Conclusions: The developed ex vivo set‐up, based on the whole porcine eye, could be suitable to perform permeation and accumulation studies of transscleral applied ocular formulations.