Polat, Heybet Kerem; Çopur, Tuğba; Pezik, Esra; Turanlı, Yasin; Karakuyu, Nasıf Fatih; Köngül, Esra; Ünal, Sedat; Gözcü, Sefa; Sarman, Emine

Objective: Allergic conjunctivitis is one of the most prevalent conditions affecting the eyes, and various medications are used in its treatment. In this study, olopatadine and verbascoside were used in combination. Methods: A factorial design was employed to evaluate the effects of Poloxamer 407 and sodium alginate. The impact of polymer concentration on parameters such as viscosity, gelation time, mucoadhesion, pH, and gelation temperature–considered indicators of ideal formulations–was assessed. Results: The optimal formulation, determined through the factorial design, included 0.5% sodium alginate and 20% poloxamer 407. The obtained values were viscosity at 25 °C = 7451.8 cP, viscosity at 35 °C = 11367.3 cP, pH = 7.12, gelation temperature = 30 °C, gelation time = 52 s, and mucoadhesion = 0.301 N. Cytotoxicity tests on ARPE-19 and L929 cells, along with irritation studies, indicated acceptable safety profiles. In vitro release tests demonstrated an initial burst release of verbascoside and olopatadine during the first 2 h, followed by a controlled release over the subsequent 8 h. Mathematical analysis of the release kinetics revealed a good fit with the Weibull model. No adverse effects were observed in rats during Draize’s in vivo test. Conclusions: Consequently, the drug-loaded in situ gel formulation may be a promising option for treating allergic conjunctivitis.

Karakuyu, Nasif Fatih; Polat, Heybet Kerem; Unal, Sedat; Haydar, Muhammet Kerim; Mokhtare, Behzad; Aykurt, Furkan; Aksit, Aleyna

Objective: The present study created nimesulide-loaded in situ gels and assessed their potential application in ocular inflammation. Methods: Because in situ gels have a low viscosity, sodium alginate, and hydroxypropyl methylcellulose combined to create a nimesulide CD complex that is easy to apply. However, due to the gelation creation with pH, washing and removing it from the ocular surface becomes challenging. Production was carried out using different ratios of sodium alginate, hydroxypropyl methylcellulose, and hyaluronic acid. Results: Characterization studies led to the determination of the optimized formulation. The optimized formulation viscosity pH 5.5 = 547.3 ± 76cP, viscosity pH 7.4 = 8798.3 ± 254 cP, and pH = 5.4 ± 0.01 were obtained. In in vitro release experiments, approximately 53% of nimesulide was released by burst action within 2 h, followed by a controlled release over 12 h. Mathematical modeling of the formulations’ release kinetics revealed that they were consistent with the Korsemeyer-Peppas and Weibull models. It was determined that nimesulide-loaded in situ gels showed over 80% viability in the L929 cell line. Rats underwent no adverse conditions in Draize’s in vivo experiment. Conclusion: For this reason, the TB5 formulation may be a good choice when treating ocular inflammation. These findings may be supported by future efficacy studies using this formulation.

Polat, Heybet Kerem; Gözcü, Sefa; Ünal, Sedat; Paçacı, Timur; Aytekin, Eren; Karakuyu, Nasıf Fatih; Köngül Şafak, Esra; Gültekin, Yakup; Yazıksız, Yonca; Kurt, Nihat

Objective: In the current research, 6-gingerol (GA)-loaded nanofiber drug delivery system were developed, and their potential usage in wound healing was evaluated. Significance: This study investigates the effectiveness of nanofibrous membranes composed of sodium alginate (SA), poly(vinyl alcohol) (PVA), and 6-gingerol (GA) as delivery systems for anti-inflammatory agents in the context of wound dressings. Methods: GA-loaded SA/PVA nanofiber was prepared using electrospinning. In vitro characterization of this nanofiber included the examination of comprehensive in vitro characterization, anti-inflammatory and antioxidant activities, cytotoxicity, a scratch tes and in vivo skin test. Results: GA was extracted from Zingiber officinale, and its successful isolation was confirmed through analyses such as H-NMR, C-NMR. Then GA was electrospuned into the SA/PVA nanofibers, and scanning electron microscopy (SEM) imaging revealed that the fiber diameters of the formulations ranged between 148 nm and 176 nm. Anti-inflammatory and antioxidant studies demonstrated that the effectiveness of GA increased with higher doses; however, this increase was accompanied by decreased cell viability. In vitro release studies revealed that GA exhibited a burst release within the first 8 h, followed by a controlled release, reaching completion within 24 h. Within the scope of in vitro release kinetics, release data are mathematically compatible with the Weibull model with high correlation. The scratch test results indicated that TB2 (%1 GA) promoted epithelialization. Furthermore, it was determined that TB2 (%1 GA) did not cause any irritation. Conclusions: As a result, TB2 shows promise as a formulation for wound dressings, offering potential benefits in the field of wound care.

Polat, Heybet Kerem; Ünal, Sedat; Aytekin, Eren; Karakuyu, Nasıf Fatih; Pezik, Esra; Haydar, Muhammet Kerim; Kurt, Nihat; Doğan, Osman; Mokhtare, Behzad

Objective: In the current research, lornoxicam-loaded in situ gels were developed, and their potential usage in ocular inflammation was evaluated. Significance: Lornoxicam cyclodextrin complex prepared with hydroxypropyl methylcellulose and poloxamer P407 because of the low viscosity of in situ gels to provide easy application. However, washing and removing it from the ocular surface becomes difficult due to the gelation formation with heat. Methods: A three-level factorial experimental design was used to evaluate the effects of poloxamer 407 concentration, polymer type, and polymer concentration on viscosity, pH, gelation capacity, gelation time, and gelation temperature, which were considered the optimal indicators of lornoxicam-containing formulations. Results: As a result of the three-level factorial experimental design, the optimized formulation contained 15 (%w/v) poloxamer 407 and 1 (%w/v) hydroxypropyl methylcellulose. The optimize formulation viscosity 25 °C = 504 ± 49cP, viscosity 35 °C = 11247 ± 214cP, pH = 6.80 ± 0.01, gelation temprature = 35 ± 0.2 °C, and gelation time= 34 ± 0.2 s was obtained. In the in vitro release studies, 68% of lornoxicam was released with a burst effect in the first three hours; then, the release continued for eight hours with controlled release. Release kinetics of the formulations were modeled mathematically, and it was found to be compatible with the Korsemeyer-Peppas and Weibull models. In cell culture studies, cell viability at 100 µg/mL was 83% and 96% for NL6 and NL6-CD, respectively. In Draize’s in vivo test, no negative conditions occurred in rats. Conclusions: Therefore, the NL6-CD formulation has the potential to be a favorable option for treating ocular inflammation.