Ocular drug delivery toxicity

De Campos, A.M., et al. 2004. Chitosan nanoparticles as new ocular drug delivery systems In vitro stability, in vivo fate, and cellular toxicity. Pharm Res 21 803. 

Liposomes can be easily prepared from non-toxic materials, which are non-irritant and do not obscure vision. Unfortunately, routine use of liposomes in topical ocular drug delivery is presently limited by short shelf life of the formulation, limited drag loading capacity and obstacles in sterilizing the preparation. 

Despite its widespread use and study during the first 60 years of the twentieth century, iontophoresis was never fully adopted as standard procedure. The lack of carefully controlled trials and the paucity of toxicity data were among the reasons that precluded its acceptance as an alternative for drug delivery. However, the last decade years have witnessed the development and optimization of the technology of ocular iontophoresis for fast and safe delivery of high drug concentrations in a specific ocular site [13]. 

Enriquez de Salamanca, A., Diebold, Y., Calonge, M., Garcia-Vazquez, C., Callejo, S., Vila, A., and Alonso, M. J. (2006), Chitosan nanoparticles as a potential drug delivery system for the ocular surface Toxicity, uptake mechanism and in vivo tolerance, Invest. Ophthalmol. Vis. Sci., 47(4), 1416-1425. 

Release rates are typically well below toxic levels, and higher concentrations of the drug are therefore achieved without systemic side effects. For chronic ocular diseases like cytomegalovirus (CMV) retinitis, implants are effective drug delivery systems. 

Ophthalmic diseases are most commonly treated by topical instillation of eye drops. These formulations evidence limitations like poor stability and efficacy, reduced cor-neal/scleral permeability, systemic toxicity and lack of compUance [2]. In this sense, the development of effective therapies for visual disorders is of high priority [1], which makes the field of ocular delivery one of the most interesting and challenging areas for pharmaceutical scientists [3]. There has been significant research directed towards the development of new systems for controlled drug delivery in ophthalmology such... 

For in vitro toxicity studies and assessment of the barrier function, drug transport, cell physiology, and metabolism as well as the development of delivery systems, cell culture models provide powerful systems for scientific research. As the corneal epithelium is the main barrier for ocular penetration, various corneal epithelial cell cultures were established besides the corneal constructs that mimic the whole cornea and serve as reductionist models for the ocular barrier. In general, two types of cell culture models are available primary cell cultures and immortalized, continuous cell lines. 

Combinations of the aforementioned delivery systems may offer the potential for increased ocular bioavailability and reduced toxicity. Stability, toxicity, and efficacy must then be evaluated for the complete formulation.An effective dosing regimen must also be developed before beginning clinical trials on a wide scale. The U.S. Food and Drug Administration is involved in evaluating these steps to provide formulations that are efficacious and safe. 

The intrascleral implant is a device that is implanted in the sclera it delivers the drug through the sclera to the intraocular tissues (Fig. 5). Transscleral delivery may be an effective method of achieving therapeutic concentrations of drugs in the posterior segment (24-27). The intrascleral implant that incorporated betamethasone phosphate (BP) successfully delivered the drug to the retina/choroid and vitreous (28). The concentration of BP was maintained at a level that should suppress inflammation in the retina-choroid for more than eight weeks, and did not produce any ocular toxicity. 

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