In this special focus issue, we turn our attention to the eye. One key aspect of drug delivery systems to the eye has been related to permeation characteristics of the cornea for novel drug delivery systems. In some cases, as with infectious diseases, it may be necessary to have suitable absorption characteristics, in other cases low absorption but high surface activity may be desirable. The eye is a challenging organ to target for most ailments, and so direct application of a therapeutic, although technically challenging in terms of formulation, is a logical approach. The articles presented in this special focus issue show the wide variety of techniques that are being used to tackle these challenges.
Vangala and coworkers investigated the aspects related to formulation and corneal permeation of ketorolac tromethamine (KT)-loaded chitosan (CS) nanoparticles. In this case, their goal was to demonstrate retention of the active on the surface of the cornea. They used a crosslinking ionic gelation method with various ratios of tri-polyphosphate (TPP) and CS, loaded with KT. By varying the ratio of these key excipients, the authors report that the final size of the nanoparticles was controlled by the ratio of CS/TPP, and that drug-loading efficiency was directly related to the concentration of the drug KT, with a maximum loading of 10 mg/mL. They confirm a significant difference in release characteristics of the drug-loaded nanoparticles when compared to a standard KT solution. Interestingly, the authors performed porcine ex vivo corneal permeation studies and were able to demonstrate that mucoadhesiveness played a useful role in retaining the drug on the eye surface, indicating the potential for this dose-delivery platform.
Liu et al. looked at improve the stability and ocular efficacy of a novel eye drop of alpha tocopherol. The system looked at a novel mixed micellular formulation as an ophthalmic delivery system for alpha-tocopherol (TOC), with the goal of improving stability and improving local efficacy. Using a thin-film hydration method, Polyoxyl 15 Hydroxystearate (Solutol®HS15) and Pluronic® F127 were demonstrated to encapsulate TOC with a 27.7% drug-loading efficiency. With the subsequent addition of cetalkonium chloride (CKC), the zeta potential of micelles was able to be adjusted to +17 mV. The authors point out this control of zeta potential allows for the possible residence time prolongation on ocular surfaces. The encapsulation of the TOC within the micelles was shown to remain stable for at least 6 months when sealed with N2. The group went on to show that the cationic micelles were well-tolerated after multiple administrations in rabbits with an improved ocular accumulation of TOC.
The next article looks at the preparation and evaluation of a sustained release timolol maleate drug–resin ophthalmic suspension. Liu and coworkers describe how a drug–resin complex was prepared using an oscillation method, and then characterized regarding particle size, zeta potential, morphology, and drug content. They conducted an in vivo study in rabbits, following in vitro drug release characterization. Using relatively large particles of 4.8 ± 1.2 µm with a drug loading at 43.00 ± 0.09%, they indicated that drug released from the drug–resin ophthalmic suspension permeated the cornea. They go on to report that drug levels in the ocular tissues after administration of the drug–resin ophthalmic suspension were significantly higher than after treatment with a standard eye drop formulation. To demonstrate the local targeting effect, the authors point out that overall drug concentrations were high in ocular tissues but were lower in body tissues and in the plasma.
Li et al. draw our attention to the leading cause of blindness in the world, cataracts. The researchers investigated the ocular delivery of cyanidin-3-glycoside in liposomes (C3G-TCL) and its prevention of selenite-induced oxidative stress. For manufacturing, the authors report a reverse-phase evaporation method before coating with self-synthesized N-trimethyl chitosan (TMC), with an encapsulation efficiency of 53.7 ± 0.2%. After conducting a series of tests to evaluate physicochemical properties, a gamma-scintigraphy study was employed to evaluate the precorneal elimination of the radioactive preparations. A greater than 3-fold increment in precorneal residence time for C3G-TCL was found when compared to a standard 99mTc-solution. Additionally, the TMC coating reportedly enhanced the transepithelial transport of liposomes to a depth of 40-μm in the cornea. The authors also indicate that C3G-TCL could significantly elevate the activity of superoxide dismutase and catalase in lens and also show a considerable reversal of reduced glutathione activity. These positive findings are encouraging when one considers the far-reaching implications of work in this field.
The final article related to the special focus issue draws our attention to infectious diseases. Ciprofloxacin is a widely used drug, active against a broad spectrum of aerobic Gram-positive and Gram-negative bacteria. Bonferoni explored the ionic interactions between ciprofloxacin and the polyelectrolytes chondroitin sulfate or lambda carrageenan, which resulted in co-precipitates. The authors report that these drug-laden co-precipitates can act as microparticulate-controlled release systems. With the addition of Carbopol, Bonferoni et al. suggested an improvement in mucoadhesive properties, with the potential for an increased drug residence time.
Overall, this special focus edition demonstrates the challenges of directing a specific therapeutic agent to the eye and having it maintained for a suitable duration, in order to both be efficacious and convenient to a broad patient population. We are provided with useful insights into innovative approaches to tackle these substantial problems related to occular therapies. As always, we thank the authors for their high-quality contributions.
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