Application of nanotechnology in both diagnostics and treatment areas in the biomedical field is more exciting than ever. Nowadays, most ocular medications on the market still contain toxic preservatives. Besides the research and development cost to develop new ocular medications with minimally toxic preservative, this required important resources to adapt the manufacturing industrial processes. Presence of a preservative in an ocular medication has often resulted in damaging the epithelium. Preservatives are an important component of ophthalmic preparations, preventing bacterial growth and subsequent infection. Benzalkonium chloride (BAK), chlorobutanol, chlorhexidine acetate (CHA), and phenylmercuric nitrate or acetate are some commonly used preservatives in eye preparations. BAK is a detergent-type preservative. It is a quaternary ammonium cationic surfactant that has a very long shelf life and is very effective against a broad spectrum of organisms. Additionally, it increases drug penetration. Unfortunately, BAK disrupts the tight junctions between human cells and accelerates desquamation of the epithelium. BAK promotes apoptosis at low concentrations and necrosis at higher concentrations.
New preservatives with a wide range of activity and good safety profiles have been introduced in the market, such as stabilized oxychloro complex (SOC). Stabilized Oxychloro Complex (SOC) (Purite) is a combination of chlorine dioxide, chlorite and chlorate which causes oxidation of intracellular lipids and glutathione, interrupting vital enzymes for cell function and maintenance. When exposed to light, Purite degrades to water, oxygen, sodium, and chlorine free radicals. Chlorine free radicals are thought to inhibit microorganism protein synthesis within cells by way of glutathione oxidation, which causes microbe cell death. It is effective at unusually low concentrations. It has demonstrated antimicrobial activity against bacteria, viruses and some fungi. Because of its propensity to generate free radicals, it is an effective oxidizer and also breaks down rapidly when exposed to the ocular surface. SOC, a non-irritating preservative is useful for ophthalmic products used chronically or with a compromised ocular surface. Non-irritating preservatives are especially needed for ophthalmic products when the treatment is chronic or when the ocular surface is compromised as in dry eye.
A case study in New Zealand has demonstrated the effects of BAK and SOC and the results are amusing. White rabbits (3/group) received in the left eye, 2 drops (6 times/day for 7 days) of 150, 250, or 500 ppm Purite(R) in 0.5% carboxymethylcellulose (CMC), 150 ppm Purite(R) in phosphate buffer, or 100 ppm BAK in phosphate buffer. The right eye served as the untreated control. The parameters evaluated were ocular discomfort, gross ocular observations, slit lamp biomicroscopy, and ocular histopathology. Treatment with 100 ppm BAK in phosphate buffer caused transient minimal ocular discomfort (43% frequency). The frequency of minimal ocular discomfort in the Purite(R) groups was 0 – 5% (p<0.001 in comparison with BAK group). Treatment with BAK caused transient mild ocular hyperemia (14% frequency), whereas no hyperemia noted in the Purite(R) treatment groups. Treatment with BAK caused minimal to mild degeneration of the corneal epithelium and minimal to mild goblet cell loss in the conjunctiva (100% incidence). By contrast, for all Purite(R) treatment groups combined, the only histopathological lesion was minimal goblet cell loss (8% incidence, p<0.001). In conclusion, it should be kept in mind that preservatives in ocular medications are toxic for the ocular surface. These effects are dose- and time-dependent and the risk to develop the ocular surface disease is increased particularly in those patients who received long-term multi-therapy with several eye drops daily like glaucoma or dry eye disease. Beyond the ocular discomfort, and the subjective problem of quality of life, chronic inflammation of the ocular surface may produce severe sight-threatening adverse effects and is an important risk factor of the filtering surgery failure. Although the priority is to treat the primary ocular disease, defects of the ocular surface may compromise the efficacy of the ocular treatment in terms of adherence to treatment. For these reasons, ophthalmologists should evaluate the risks and benefits of ophthalmic medications before initiating therapy, identify the minimum dosages necessary to achieve a therapeutic benefit, and monitor patients for ocular surface disease. Physicians should consider treatment with new-generation preparations containing low-risk preservatives such as SOC, especially in patients receiving multiple ophthalmic medications.