Akne Tedavisi için İlaç Yüklü Mikroiğneli Yamaların Geliştirilmesi

Abstract

Acne vulgaris is a common and chronic disease, especially during adolescence, due to various factors such as inflammation of the pilosebaceous units of the skin, colonization of the Propionibacterium acnes bacterium, activity of sebaceous (oil) glands, genetic factors, lifestyle and hormones. In the treatment of acne, the combination of oral or topical antibiotics and retinoid drugs is the most effective option. Today, these drugs are available in traditional forms such as tablets, creams and gels. In recent years, microneedle (MN) patches have been considered as ideal platforms for the transdermal delivery of various therapeutics, primarily due to their enhanced penetration properties. This thesis aim to design and produce microneedle patches by loading them with tetracycline (TCH), commonly used in acne treatment, and a retinoid derivative known as retinoic acid (RA) in a hydrogel structure. To achieve this, microneedles based on gelatin (Gel) and poly(vinyl alcohol) (PVA) were fabricated using a micro-molding technique. The microneedles were loaded with tetracycline and retinoic acid at different doses, characterized and their effectiveness evaluated. The morphologies of the produced microneedles were examined using light and scanning electron microscopy (SEM). Microscopic images revealed that square-based pyramidal microneedles with a height of approximately 650 μm exhibited well-defined structures, and the active substances were successfully loaded onto the microneedles. The thermal properties of the microneedles were investigated using Differential Scanning Calorimetry (DSC) and Thermogravimetric Analysis (TGA). It was observed that all samples exhibited thermal degradation approximately at 325 °C, with mass losses of around 76-82% in the temperature range of 300-450 °C. Adding the active substances to the Gel/PVA did not significantly affect thermal degradation. DSC thermograms of the microneedles showed similar characteristics, with two different glass transition temperatures (Tg) identified: one at 37.5 °C attributed to PVA and another at 49.22 °C attributed to gelatin. Additionally, the melting temperatures of gelatin and PVA were observed at 110°C and 195.36 °C, respectively. The microneedle patches did not exhibit toxic effects against the L929 cell line. A penetration test of the microneedles was performed using parafilm layers, and it was determined that microneedles with a height of 650 μm reached approximately the 5th to 6th parafilm layer. Based on these results, it can be concluded that the microneedles can penetrate into the dermal layer of the skin. The antibacterial activity of the prepared microneedle patches was examined against Staphylococcus aureus ATCC 29213 strain, and they were found to possess antibacterial properties. In conclusion, hydrogel-based microneedle patches loaded with tetracycline and retinoic acid have the potential to enhance penetration and are considered for use in the topical treatment of acne vulgaris through a combined drug approach.