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    Design and characterization of dexamethasone loaded microsponges for the management of ulcerative colitis
    (Elsevier, 2023) Özdemir, Samet; Üner, Burcu; Baranauskaite, Juste; Sümer, Engin; Yıldırım, Ecem; Yaba, Aylin
    Ulcerative colitis is an inflammatory condition with ulcerations throughout the colon. The existing remedies have some limitations such as drug inactivation, poor absorption, and adverse reactions. The present study aimed to design novel microsponge formulations to enhance remission of the dexamethasone (as a model pharmaceutical ingredient) in the colon. Microsponges were prepared by using the quasi-emulsion technique. The optimal formulation was selected by applying the design of experiments approach which used methylcellulose (MC) (0.75–2%, w/w), polyvinylalcohol (PVA)(0.5–1%, w/w), and tween 80 (TW80) (1.5–2.5%, w/w). The critical quality attributes were selected as particle size and entrapment efficiency. The particle size and encapsulation efficiency were found as 140.38 ± 9.2 µm and 77.96 ± 3.4 %. After the optimization; morphological, thermal, and physicochemical characterization studies were performed. Ultimately, the optimal formulation was investigated by using the acetic acid-induced ulcerative colitis model in rats. The physicochemical characterization studies confirmed that the formulation components were compatible with each other. The in vitro release mechanisms were fitted to First order kinetics at pH 1.2 (R2:0.9563), and Korsmeyer-Peppas kinetics at pH 4.5 (R2: 0.9877), and pH 6.8 (R2: 0.9706). The medicated microsponges exhibited remarkable recovery compared to the control group of the in vivo ulcerative colitis model (p < 0.05). It could be concluded that microsponges were evaluated as a promising alternative drug delivery system for the management of ulcerative colitis.
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    Loteprednol loaded nanoformulations for corneal delivery: Ex-vivo permeation study, ocular safety assessment and stability studies
    (Editions de Sante, 2023) Üner, Burcu; Özdemir, Samet; Yıldırım, Ecem; Yaba, Aylin; Taş, Çetin; Üner, Melike; Özsoy, Yıldız
    Purpose Loteprednol etabonate (LE) is a topical corticosteroid that is used in inflammatory and allergic conditions of the eye. Nanoformulations including solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), and nanoemulsion (NE) of LE were prepared for increasing its ocular bioavailability and minimizing the risk of side effects. Methods Nanoformulations were prepared using hot emulsification and ultrasonication technique. The stabilities of the SLN, NLC, and NE were studied at different thermal conditions for 180 days. In this context, alterations in particle size (PS), zeta potential (ZP), viscosity, pH, %EE, and thermal behavior of the formulations were determined. Ex vivo corneal permeation study was performed, subsequently, the tape stripping approach was conducted for defining the LE amount that was blocked by the tear film layer. In addition, to determine the LE amount in epithelial tissue, a homogenization test was performed. Results the PS of the formulations was between 82.23 and 126.9 nm, and ZPs were between −20.8 mV and −24.6 mV. Furthermore, SLN, NLC, and NE formulations were found to be 2.05, 1.86, and 1.39 times higher LE retained in the cornea against the marketed product, respectively. Conclusion SLN, NLC, and NE might be alternative delivery systems by reducing the amount of LE for each dose and being used safely based on the results both of MTT and histopathological examinations as well.
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    The effect of rapamycin treatment on mouse ovarian follicle development in dehydroepiandrosterone-induced polycystic ovary syndrome mouse model
    (Zygote, 2024) Yıldırım, Ecem; Önel, Tuğçe; Aguş, Sami; Günalan, Elif; Yılmaz, Bayram; Aydın, Mehmet Şerif; Yaba, Aylin
    Polycystic ovary syndrome (PCOS) is a complex reproductive and endocrine disorder affecting 5–10% of women of reproductive age, but the pathophysiology of PCOS still remains unknown. Here, the aim of our study was to analyze the effects of rapamycin treatment that may regulate impaired hormonal levels and folliculogenesis in dehydroepiandrosterone (DHEA)-treated PCOS mouse. We hypothesized that rapamycin may ameliorate the negative effects of PCOS in DHEA-induced PCOS mouse model. The target of rapamycin (TOR) gene product is a serine/threonine kinase that has been implicated in the control of cell growth, proliferation and autophagy, and rapamycin is a potent inhibitor of mTORC1 pathway. In this study, for the first time, mTORC1 and activation products are presented at protein and mRNA levels after rapamycin treatment in DHEA-induced PCOS mouse ovary. We showed that rapamycin treatment may regulate follicular development, hormonal levels and provide ovulation in DHEA-induced PCOS mouse. Additionally, we assessed decreased primordial follicle reserve, increased number of primary and secondary follicles, corpus luteum structure forms again after 10 days of rapamycin treatment. This study presented here suggests rapamycin treatment regulates hormonal phenotype and folliculogenesis in the ovary and also mTOR signalling pathway in granulosa cells of DHEA-induced PCOS mouse ovary which may have potential to attenuate understanding the mechanism of dominant follicle selection and anovulatory infertility.