Kendini iyileştirebilen hidrojel esaslı kontakt lens malzemesi geliştirilmesi
Development of self-healing hydrogel based contact lens material
Yazar: BÜŞRA KAŞAĞICI
Danışman: PROF. DR. MAHMUT ÖZACAR
Sakarya Üniversitesi / Fen Bilimleri Enstitüsü / Biyomedikal Mühendisliği Ana Bilim Dalı
Derece: Yüksek Lisans, 2023
Konu: Biyomühendislik = Bioengineering ; Kimya = Chemistry ; Mühendislik Bilimleri = Engineering Sciences

Özet:
Görme bozukluklarının en yaygın sebeplerinden birisi kırma kusurlarıdır ve bu rahatsızlık küresel bir halk sağlığı sorunu olarak kabul edilmektedir. Bu kusurları düzeltmek için genellikle gözlük veya günümüzde kullanımı yaygınlaşan kontakt lensler kullanılmaktadır. Kontakt lenslerin gözlükle kıyaslandığında daha doğal bir görüş izlenimi verdiği ve kırma kusurlarını düzeltmeye yönelik olarak tasarlanan optik tıbbi cihazlar olduğu söylenebilir. Kontakt lenslerin kullanıcı rahatını korurken iyi dayanıklılık ve kullanım süresi gibi gelişmiş işlevlere sahip olması beklenir. Bu özellikleri sağlamak amacıyla çeşitli malzeme türleri geliştirilmiştir ve hala bu konu üzerinde çalışmalar devam etmektedir. Zayıf görmeye neden olması, göze rahatsızlık vermesi gibi sebeplerle insanlar kontakt lens kullanmayı bırakmaktadır. Bunun dışında insan vücudunda sıkça göz hastalıkları meydana gelmekte ve bu hastalıklar çoğunlukla ilaçlar vasıtasıyla tedavi edilmektedir. Ancak ilaçlar tedavi edici kullanımlarda, vücut üzerinde bazı yan etkiler gösterebilmekte ve yoğunlukları çok fazla olduğunda normal dokulara zarar verebilmektedir. Ayrıca göz damlası, toz ve merhem içeren ilaçların geleneksel uygulamalarının, düşük geçirgenlik, kısa kalma süresi, düşük biyoyararlanım gibi sınırlamaları olduğu görülmektedir. Oftalmik yolla ilaç dağıtımında ilacı gözde daha uzun süre tutmanın ve biyoyararlanımın arttırılmasının sağlanması ilaç salımlı kontakt lens kullanılmasıyla gerçekleştirilebilmektedir. Polivinil alkolden üretilen hidrojeller korneadeki ilaç dağıtım uygulamaları için sıkça tercih edilmektedir ve su tutma kapasitesi de oldukça iyidir. Yapılan çalışmada polivinil alkol bazlı hidrojel kontakt lens malzemeleri geliştirilmiştir. Polivinil alkol, dimetil sülfoksit ve gliserol ilave edilerek kontakt lens malzemesi olarak kullanılmak üzere hidrojel malzemeler geliştirilmiştir. Daha sonra katkı malzemesi kullanılarak bu malzemelerin hidrojeller üzerindeki etkisi araştırılmıştır. Oluşturulan hidrojel malzemelerin kontakt lens olarak kullanılabilirliğini incelemek amacıyla kendini iyileştirme özellikleri, antibakteriyel aktiviteleri, şişme özellikleri, su tutma özellikleri, oksijen geçirgenlikleri, ilaç salım özellikleri, temas açısı özellikleri, FTIR ve SEM analizleri yapılmıştır. Yapılan testler sonucunda katkı malzemesi kullanılarak üretilen hidrojellerin, hidrojel yapısını bozmadığı ve özellikle katkı malzemesi kullanılarak üretilen hidrojel malzemenin katkı maddesi olmadan üretilen hidrojel malzemeden daha üstün özelliklere sahip olduğu düşünülmektedir. Borik asit ve ilaç ilave edilen hidrojel kontakt lens malzemesinin, kontakt lens kullanımı açısından kapsamlı araştırmalar için potansiyel göstereceği düşünülmektedir.

Abstract:
One of the most common causes of visual impairment is refractive error, and this disorder is recognized as a global public health problem. To correct these defects, glasses or contact lenses, which are widely used today, are generally used. It can be said that contact lenses give the impression of a more natural vision compared to glasses and are optical medical devices designed to correct refractive errors. Contact lenses are expected to have advanced functions such as good durability and wear time while maintaining wearer comfort. Various material types have been developed to provide these properties and studies are still ongoing on this subject. In some cases, people stop using contact lenses for reasons such as poor vision and eye discomfort. The materials chosen for contact lenses are very important in terms of being a solution to these problems. One of the preferred materials in soft contact lens design is hydrogels. Hydrogels have the ability to absorb and swell very high volumes of water, yet remain fit for design because they remain intact. Apart from high water absorption and water holding capacity, hydrogels have a porous structure. It may also resemble living tissues and be easily adapted. When all the properties of hydrogels are examined, it is seen that they have unique properties. Thanks to these unique properties, hydrogels are crucial for biomedical applications, including drug delivery systems. Apart from this, eye diseases occur frequently in the human body and these diseases are mostly treated with drugs. However, in therapeutic use, drugs can show some side effects on the body and can damage normal tissues when their concentration is too high. In addition, conventional applications of drugs containing eye drops, powders and ointments seem to have limitations such as low permeability, short residence time, and low bioavailability. In ophthalmic drug delivery, keeping the drug in the eye for a longer time and increasing the bioavailability can be achieved by using drug-releasing contact lenses. Polyvinyl alcohol hydrogels, which have been the subject of frequent research in recent years, are considered to be the most useful hydrogel in terms of biomedical materials when examined comprehensively. Hydrogels produced from polyvinyl alcohol are frequently preferred for drug delivery applications in the cornea and have a very good water holding capacity. Polyvinyl alcohol is generally crosslinked using a physical method of repeated freeze-thaw cycles to form stable hydrogels with high swelling capacity. In the study, it was aimed to develop contact lens material created using polyvinyl alcohol. Hydrogel materials have been developed to be used as contact lens materials by adding polyvinyl alcohol, dimethyl sulfoxide and glycerol. Then, the effect of these materials on hydrogels was investigated by using additives. Boric acid and triton X-100 were preferred to examine its contribution. In addition, the properties of hydrogels were investigated by adding drugs. Especially in recent years, there has been a rapid development in boric acid chemistry. Boric acid is a weak acid and is inorganic. Boric acid is very water soluble, commercially available, recyclable, lightweight and environmentally friendly. These properties of boric acid attract attention and become the reason for preference in many areas. Since boric acid does not cause any toxic effects when used in low concentrations, it is considered both easy and safe to use. Materials that immediately give hydrophobic properties when dissolved in a liquid, have a certain surface activity, and change the surface energy of the solvents they dissolve in a high amount even at low densities are generally defined as surface active materials. Triton X-100 is also one of the surfactants. In the study, it is aimed that the boric acid additive contributes to the antibacterial activity without impairing the hydrogel properties and the properties related to drug release, while triton X-100 material is aimed to reduce the contact angle. Hydrogel materials were developed without additives and using additives, and in order to examine the usability of hydrogel materials as contact lenses, their self-healing properties, antibacterial activities, swelling properties, water retention properties, oxygen permeability, drug release properties, contact angle properties, fourier transform infrared spectroscopy and scanning electron microscopy analyzes were made. In addition, in order to see the similarity and appearance of the hydrogel contact lens material samples prepared in the study, using a three-dimensional printer, contact lens molds were produced to pour the hydrogel samples into it and form the contact lens shape. The prepared hydrogel samples were poured into these prepared molds while they were in liquid form, and materials in the form of contact lenses were produced using the freeze-thaw method. The scratch test was used to test its self-healing properties, and the hydrogel samples cut at certain proportions were left to wait at specified time intervals by making scratches from one end to the other, and then the samples were placed in the freezer. The closure conditions of the scratches were examined under an optical microscope and the self-healing properties of the hydrogels were interpreted. Staphylococcus aureus and pseudomonas aeruginosa bacteria were selected for antibacterial testing of hydrogels whose usability as contact lens material will be examined. Hydrogel samples with and without additives were kept in agar-coated petri dishes and their antibacterial activities were interpreted. Hydrogel samples were cut at certain ratios in terms of swelling properties and water retention properties and their initial weights were measured using precision balances. Then, for the swelling test, the hydrogel samples were kept in distilled water and artificial tear fluid and their weights were measured again at certain hour intervals. For their water holding properties, the hydrogels were kept at ambient temperature and interpreted by measuring their weight at certain time intervals. Low oxygen permeability in contact lenses can cause significant side effects. Oxygen cannot reach the human eye sufficiently through the vascular system. For this reason, oxygen reaches the human eye through contact with air. Appropriate contact lens wear is required to ensure the exchange of oxygen and carbon dioxide. Soft contact lenses with low oxygen permeability may also cause loss of corneal transparency and block the flow of oxygen to the cornea. The swelling test results were used for the oxygen permeability test, and the oxygen permeability of the contact lens material produced accordingly was compared with the literature and interpreted. In order to examine the drug release properties, samples with drug additives were selected for contact lens materials. In order to perform drug release tests, a calibration curve was created and the drug release measurements of the hydrogel samples, which were kept in the prepared phosphate buffer solution, were taken using ultraviolet-visible spectrophotometer. Other characterization tests were performed and interpreted using instruments used in the laboratory. As a result of the tests, it was observed that the hydrogels produced using additives did not degrade the hydrogel structure. However, it has been observed that the hydrogel material produced with the additive of triton X-100 will not be suitable for use as a contact lens material because it slightly impairs the transparency of the material. In hydrogel contact lens materials produced with boric acid additive, it is thought that the amount of boric acid added is important and the antibacterial effect of the hydrogel materials does not change much as the amount of boric acid increases, but when the other properties are compared, the hydrogel samples with a lower percentage of boric acid have superior properties. It was observed that the use of drugs did not disrupt the structure of the hydrogel contact lens material. It is thought that especially hydrogel contact lens material, which contains both drug additives and 1% boric acid additive, will have superior properties compared to other samples and will show potential in terms of use as contact lenses by conducting extensive research and in vivo studies.