Recent Progress of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers as Ocular Drug Delivery Platforms

According to World Health Organization, the prevalence of eye conditions is expected to increase in the following years as a result of population aging, the associated rise of non-communicable diseases (diabetes, cardiovascular diseases), along with various lifestyle factors, such as an unhealthy diet, smoking, extensive usage of digital devices, etc. [1,2,3,4]. Furthermore, a recent analysis for the Global Burden of Disease Study forecasts that by 2050, around 474 million people will suffer from moderate to severe visual impairments, among which 61 million will develop complete blindness [5]. Although the human eye is one of the most accessible organs in terms of drug application, efficient ocular delivery is still a goal to be achieved. Possible explanations lie in the anatomical and physiological characteristics of the eyeball and its protective mechanisms, as well as in the technological properties of the ocular formulations [6]. According to location, the human eye may be distinguished into two segments: anterior, presented by the cornea, conjunctiva, iris, ciliary body, lens, and aqueous humor, and posterior, consisting of the sclera, choroid, retina, vitreous humor, and optic nerve [7,8]. The preferred route of administration in ophthalmology—topical instillation—provides the possibility for treatment of anterior segment diseases such as blepharitis, dry eye disease, conjunctivitis, ocular infections or injuries [9], however, reaching the posterior part of the eye and ensuring sufficient therapeutic concentration thereby is still a challenge. Eye drops, representing the majority of ophthalmic formulations, are relatively easy for self-administration, characterized by high patient approval, cost-effectiveness, and well-established formulation and manufacturing processes [10]. Their main limitations include their intrinsic low viscosity, a short ocular contact time, and the relatively large volume of applied drops, often leading to drug loss via physiological pathways [11,12,13].

Additionally, ocular defense mechanisms such as reflex blinking, tear turnover, nasolacrimal drainage, and static and dynamic anatomical barriers further hinder drug absorption, resulting in less than 5% of the instilled dose attaining deeper ocular tissues [14,15]. In ocular surface diseases, drug bioavailability may be partially improved through modulating the formulations’ viscosity, by including viscosity enhancers or using in situ gel-forming systems/semisolid dosage forms [16]. However, this strategy does not apply to posterior segment diseases. Unfortunately, diseases affecting the back part of the eye, e.g., age-related macular degeneration, diabetic retinopathy, and glaucoma, may often cause visual impairment or blindness unless treated efficiently [17,18]. The therapy of posterior segment eye diseases usually includes intravitreal injections, which enable drug delivery to the vitreous cavity. However, the invasive nature of this approach and the potential associated complications (e.g., endophthalmitis, retinal detachment) determine the low patient compliance [19,20]. Reaching the posterior segment via the peroral or intravenous route has also been associated with limited therapeutic success, due to the presence of blood–ocular barriers (the blood–retinal barrier, in particular), in addition to the potential risk of occurrence of side effects [21].

Altogether, these factors determine the necessity of further progress in the field of ocular delivery by improving the technological characteristics of conventional ophthalmic formulations, exploring advanced drug delivery systems, or combining both strategies. Various nanoscale drug delivery systems, such as liposomes [22,23], niosomes [24,25], solid lipid/polymeric nanoparticles [26,27,28,29], nanostructured lipid carriers [30,31], nanomicelles [32,33], microemulsions [34,35], and dendrimers [36], have been successfully developed for ocular delivery purposes, and have been reported to achieve enhanced bioavailability, sustained and controlled drug release, and a reduction in the number of applications, as well as side effects. SLNs and NLCs raise great interest due to their excellent biocompatibility and tolerability, tunable physiochemical characteristics, and scaling-up capabilities [37,38,39].

Developed for the first in the 1990s by Professor Müller and Professor Gasco, SLNs represent a mixture of solids at ambient temperature and and lipids at physiological temperatures, dispersed in an aqueous phase containing surfactants [40,41]. Approximately 10 years later, a second generation of lipid nanoparticles was proposed—NLCs,—which additionally include liquid lipid(s) in their structure [42,43]. Both drug delivery systems are feasible carriers for hydrophilic and hydrophobic drugs. They are characterized by their long-term stability and favored uptake through biological membranes, owing to their lipid nature and nano dimensions [44,45]. The possibilities to impart mucoadhesiveness by surface coating with various polymers, or by incorporating them into semisolid/in situ gelling/formulations, further promotes their beneficial effects in ocular therapeutics.

The current review aimed to summarize the recent research progress of solid lipid nanoparticles and nanostructured lipid carriers in ocular delivery. In the first part, the anatomical and physiological features of the human eye and potential delivery routes have been discussed. The second part provides an overview of the specific characteristics of SLNs and NLCs, with respect to their compositions, suitable physicochemical properties tailored for effective ocular delivery, surface modification strategies, and sterilization feasibility. Recent advances in this area have also been outlined.