(670d) Contact Lenses Prepared By Using the Layer-By-Layer Method for Sustained Drug Delivery

It is known that a lot of the people are suffering from eye diseases. Approximately 90% of the drug formulation is implemented as eye drops in topical implementation^[1]. However, bioavailability of the eye drop is too low and only 1-5% of the drug can reach the target tissue. The remaining drug is thrown away from the nasal cavity and discarded drugs can cause serious side effects^[2]. Researchers has developed various approaches to eliminate these disadvantages of the use of eye drops in recent years. Increasing the viscosity and permeability of eye drops or loading drugs into micro and nano particles or into contact lenses are some of the approaches that have been studied. Among the others, contact lense based drug delivery systems have two basic advantages such as minimizing the side effects of drugs used excessively and elimination of drug loss/waste^[3].

A Synthetic polymer p-HEMA is used frequently for controlled release applications as well as being used as a soft material. There are few studies that focus on usage of p-HEMA contact lenses to achieve prolonged drug release. Even though, they are more successful than eye drops and ointment, sustained drug release cannot be provided as desired. Drug loaded p-HEMA contact lenses release the drug in few hours. There are some methods used to slowdown the drug release^[4]. One of these methods is utilizing the layer by layer method in order to modify the surface of the p-HEMA hydrogels. This method is based on the affinity between complementary functional groups^[5].

In this study it is aimed to use the drug loaded p-HEMA contact lenses for the treatment of the conjunctivitis, which is one of the common eye diseases. Conjunctivitis is inflammation of conjunctiva and the membrane layer of eyelid on inner surface. Dexamethasone is a hydrophobic drug used for conjunctivitis treatment which was added into hydrogels. The surface of hydrogels was modified via â??â??Layer by Layerâ??â?? (LbL) technique. By using this technique, it is possible to obtain up to ten layers. Moreover, a thick layer of drug free biodegradable materials were added on the top of the contact lenses, which already had five layers formed via LbL technique, as mentioned before. The formation of each layer was monitored by measuring absorbance, light transmittance and water contact angle of the lenses. Hydrogels were characterized by using FT-IR (Fourier Transform Infrared Spectroscopy), DSC (Differential Scanning Calorimetry) and SEM (Scanning Electron Microscope). Drug release concentration was measured by using UV-vis spectroscopy. It was determined that, p-HEMA hydrogel released around 60 % of the drug in 8 h. Hydrogels prepared by LbL methods (5 layers) have sustained drug release in which only 30 % of drug was released in 50 hours. It was demonstrated that the formed biodegradable material layers act as a barrier for drug release. Furthermore, addition of the drug-free layers on top of this surface modified hydrogels at different thickness gave rise to further reduction at the drug release. As a unique result, for the first time in literature, it is seen that addition of biodegradable material layer on the top of the surface modified hydrogels had allowed us to observe a â??delay timeâ?. The observed delay time varied with the changing thickness of the layer applied. The delay time increased from 15 minutes to 45 minutes with increasing thickness. Thus, controlled drug release was accomplished. Moreover, addition of biodegradable materials layer on top of the contact lenses allowed us to see a delay time before the release of drug as well as it prevented the burst release. Also, side effects of the drug were eliminated which was released at the beginning.

This study shows clearly that combining the distinct properties of different materials by using LbL method has been an effective approach for the controlled release of ophthalmic drugs. The dose of drug, which each patient must receive according to his/her drug regimen, can be adjusted by varying the thickness or the changing the number of the layers applied.

REFERENCES

[1] C. Le Bourlais, L. Acar, H. Zia, P.A. Sado, T. Needham, R. Leverge, 1998, â??Ophthalmic Drug Delivery Systems - Recent Advancesâ??, Progress in Retinal Eye Research, 17(1),33-58.

[2] J.C. Lang, 1995, â??Ocular Drug-Delivery Conventional Ocular Formulationsâ??, Adv Drug Deliver Rev, 16(1), 39-43.

[3] Y. Kapoor, J.C. Thomas, G. Tan, V.T. John, A. Chauhan, 2009, â??Surfactant-laden soft contact lenses for extended delivery of ophthalmic drugsâ??, Biomaterials, 30, 867â??878.

[4] D. Gulsen, A. Chauhan, 2004,â??Ophthalmic Drug Delivery through Contact Lensesâ?? Investigative Ophthalmology & Visual Science, 45(7), 2342-2347.

[5] X. H. Hu, Y. S. Zhang, 2014, Synthesis and surface modification of chitosan containing hydrogel for ophthalmic drug delivery, â??Materials Technology: Advanced Performance Materialsâ??, 29(3).