Farmasötik Teknoloji Ana Bilim Dalı Koleksiyonu

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https://hdl.handle.net/20.500.13055/39

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Nanoemulsions: New approaches in cancer therapy with herbal terpenes and essential oils
(Springer Nature, 2023) Seyhan, Vildan; Özdemir, Samet; Barla Demirkoz, Aslı; Üner, Melike; Rezaei, Nima
Herbal remedies have become even more popular in recent years, as they are of natural origin and their therapeutic effects have been reported by scientific researches. Herbal origin substances and products can be preferred by many health authorities as an alternative to synthetic or semi-synthetic molecules in treatment of a lot of diseases. Terpenes, a type of natural bioactives, and essential oils rich in terpenes are valuable compounds and products especially in pharmaceutical industry. Nanoemulsions have been used for years in treatment. While conventional emulsions are suitable for topical and extraparenteral applications, nanoemulsions allow parenteral application of active substances thanks to their droplet size at nanometer level. These sophisticated drug delivery systems attract increasing attention of scientists and pharmaceutical companies due to their various advantages over conventional dosage forms. Nanoemulsions were first introduced to the pharmaceutical market as parenteral nutrition products. Intralipid® (intravenous fat emulsion for infusion) is the first nanoemulsion approved for parenteral nutrition in Europe. Then, research groups focused on drug incorporation into nanoemulsions and their benefits in treatment of various diseases. High payload of lipophilic substances and materials, stability during pharmaceutical processes (such as autoclaving, lyophilization, sterile filtration) and storage, intoxicity and biocompatibility, and effective therapy by targeting and/or modifying drug delivery have been reported as outstanding advantages of nanoemulsions. Pharmaceutical application of herbal remedies and extracts is limited due to their low solubility and permeability. Nanotechnology could offer smart solutions for these drawbacks by using drug carrier systems in nanometer size range. Nanoemulsions are reported as alternative delivery systems for herbal remedies and extracts. Moreover, droplet size of the nanoemulsions provides effective absorption for low permeable herbal bioactives. Basic principles of lipid nanotechnology and targeting strategies of nanoemulsions for delivery of lipophilic substances and materials for the treatment of cancer are mentioned in this chapter. Increasing therapeutic potential of plantderived terpenes and essential oils in cancer treatment by preparing their nanoemulsions is presented by evaluating the data collected from scientific studies.
Prolonged release niosomes for ocular delivery of loteprednol: Ocular distribution assessment on dry eye disease induced rabbit model
(Springer, 2024) Özdemir, Samet; Üner, Burcu
Loteprednol etabonate (LE) is a topical corticosteroid for the symptomatic management of ocular conditions, encompassing both allergic and infectious etiologies. Owing to the dynamic and static barriers of the eye, LE exhibits signifcantly low bioavailability, necessitating an increase in the frequency of drug administration. The objective of this study is to overcome the limitations by developing niosomal systems loaded with LE. Design of Experiments (DoE) approach was used for the development of optimal niosome formulation. The optimal formulation was characterized using DLS, FT-IR, and DSC analysis. In vitro and ex vivo release studies were performed to demonstrate drug release patterns. After that HET-CAM evaluation was conducted to determine safety profle. Then, in vivo studies were carried out to determine therapeutic activity of niosomes. Zeta potential (ZP), particle size, polydispersity index (PI), and encapsulation efcacy (EE) were -33.8 mV, 89.22 nm, 0.192, and 89.6%, respectively. Medicated niosomes had a broad distribution within rabbit eye tissues and was absorbed by the aqueous humor of the bovine eye for up to 6 h after treatment. Cumulative permeated drug in the bovine eye and rabbit eye were recorded 52.45% and 54.8%, respectively. No irritation or hemorrhagic situation was observed accord ing to the results of HET-CAM study. Thus, novel LE-loaded niosomal formulations could be considered as a promising treatment option for the dry-eye-disease (DED) due to enhanced bioavailability and decreased side efects.
Nanodelivery approaches of phytoactives for skin cancers: Current and future perspectives
(Bentham Science Publishers, 2024) Alğın Yapar, Evren; Nur Özdemir, Merve; Durgun, Meltem Ezgi; Akbal Dağıstan, Özlem; Cavalu, Simona; Özsoy, Yıldız; Kartal, Murat
In recent years, there has been an increase in skin cancers due to external factors, especially environmental factors, and studies on treatment alternatives have gained importance. Nanomaterials are common, from sunscreen formulas to formulations designed to treat skin cancers at various stages. Using bioactives has multiple effects in treating skin cancers, which provides many advantages. In this regard, many phytochemicals gain importance with their antioxidant, anti-proliferative, anti-inflammatory, antiangiogenic, and analgesic effects. Their delivery with nanocarriers is on the agenda for phytochemicals to gain the targeted stability, effectiveness, and toxicity/safety properties. This review presents types of skin cancers, phytochemicals effective in skin cancers, and their nanocarrier-loaded studies from an up-to-date perspective.
Vesicular drug delivery systems: Promising approaches in ocular drug delivery
(MDPI, 2024) Batur, Eslim; Özdemir, Samet; Durgun, Meltem Ezgi; Özsoy, Yıldız
Ocular drug delivery poses unique challenges due to the complex anatomical and physiological barriers of the eye. Conventional dosage forms often fail to achieve optimal therapeutic outcomes due to poor bioavailability, short retention time, and off-target effects. In recent years, vesicular drug delivery systems have emerged as promising solutions to address these challenges. Vesicular systems, such as liposome, niosome, ethosome, transfersome, and others (bilosome, transethosome, cubosome, proniosome, chitosome, terpesome, phytosome, discome, and spanlastics), offer several advantages for ocular drug delivery. These include improved drug bioavailability, prolonged retention time on the ocular surface, reduced systemic side effects, and protection of drugs from enzymatic degradation and dilution by tears. Moreover, vesicular formulations can be engineered for targeted delivery to specific ocular tissues or cells, enhancing therapeutic efficacy while minimizing off-target effects. They also enable the encapsulation of a wide range of drug molecules, including hydrophilic, hydrophobic, and macromolecular drugs, and the possibility of combination therapy by facilitating the co-delivery of multiple drugs. This review examines vesicular drug delivery systems, their advantages over conventional drug delivery systems, production techniques, and their applications in management of ocular diseases.
Nanoemulsions as a promising carrier for topical delivery of etodolac: Formulation development and characterization
(MDPI, 2023) Özdemir, Samet; Üner, Burcu; Karaküçük, Alptuğ; Çelik, Burak; Sümer, Engin; Taş, Çetin
This research primarily focuses on the development of innovative topical nanoemulsions for etodolac, aimed at surmounting its inherent limitations. The preparation of etodolac nanoemulsions is accomplished through a combination of high shear homogenization and ultrasonication methods. The optimization of the formulation components is systematically conducted using the design of experiments methodology. The droplet size (DS), polydispersity index (PDI), and zeta potential (ZP) of the optimized formulation were assessed using the differential light scattering (DLS) technique. Surface morphology examinations were conducted using electron microscopy, while interactions between excipients and the drug were analyzed through FTIR analysis. Additionally, in vitro release and ex vivo permeability studies were carried out. Furthermore, anti-inflammatory activity was evaluated in the context of a carrageenan-induced paw edema model in rats. The DS, PDI, and ZP of the optimal formulation were 163.5 nm, 0.141, and −33.1 mV, respectively. The in vitro release profile was assessed as a sustained release by following a non-Fickian drug transport. The flux of etodolac nanoemulsions and coarse dispersions were 165.7 ± 11.7 µg/cm2 h and 59.7 ± 15.2 µg/cm2 h, respectively. Enhanced edema inhibition was observed at 13.4%, 36.5%, and 50.65% for the 6th, 8th, and 24th hours, respectively. Taken together, these results confirmed that nanoemulsions are promising carriers for the topical delivery of etodolac.
Determination of the toxicity preferences of ocular drug delivery system by comparing two different toxicity bioassays
(Mary Ann Liebert, 2023) Üner, Burcu; Durgun, Meltem Ezgi; Özdemir, Samet; Taş, Çetin; Üner, Melike; Özsoy, Yıldız
Ocular drug delivery methods are highly favored for boosting bioavailability, patient compliance, and lower adverse effects and dose frequency. In addition to preventing adverse effects from the active ingredient, the parts of drug delivery systems must be nontoxic and nonallergic as well. Mitochondrial toxicity test (MTT) and Hen's egg chorioallantois membrane (HET-CAM) assay are the most often utilized tests based on this dilemma. The toxicity of loteprednol etabonate loaded solid lipid nanoparticles, lipid nanostructured carriers, and nanoemulsion were compared. Oleic acid, Precirol®ATO5, and Pluronic® F68 were used in the preparation. Their toxicities were evaluated by using two different toxicity tests (MTT and HET-CAM). The results suggest that there are no significant differences between the HET-CAM and MTT assays. It is noteworthy that the HET-CAM assay offers a more cost-effective and environmentally friendly alternative to the MTT assay, as it does not require cell culture and generates less toxic waste. This information may be useful to consider when selecting between the two assays.
In vitro antileishmanial activity of Lavandula angustifolia essential oil on leishmania infantum parasites
(Istanbul University, 2023) İşlek, Zeynep; Şahin, Fikrettin
Objective: Leishmaniasis is an endemic tropical disease that is disseminated through the bite of a sandfly infected with Leishmania parasites. Conventional antileishmanial drugs are mainly toxic and can be ineffective; therefore, there is a need for new natural drug candidates. This study investigated the antileishmanial effects of Lavandula angustifolia (LA) essential oil on Leishmania infantum (L. infantum) parasites, and the safety features were tested on RAW264.7 murine macrophages. Materials and Methods: LA essential oil was produced through the process of hydro-distillation, and its phytochemical content was determined using the gas chromatography-mass spectrometry (GC-MS) analysis. The antileishmanial effects of LA (0.063 to1 µL/mL) on L. infantum parasites as well as their safety features were assessed on RAW264.7 murine macrophages. Results: The composition of LA essential oil was detected using GC-MS analysis, including linalool, pinene, 1, 8-cineole, linalyl acetate, and lavandulol. Concentrations at and above 0.5 µL/mL LA indicated a significant reduction (71% decrease) in the parasite proliferation, and caused a slight reduction in macrophage viability to 70% at 72 h. Conclusions: The findings revealed the antileishmanial effect of LA on L. infantum parasites with relatively less toxicity on macrophages. The promising antileishmanial efficacy highlights the potential for further in vivo studies.
Timolol-loaded ethosomes for ophthalmic delivery: Reduction of high intraocular pressure in vivo
(Elsevier, 2023) Üner, Burcu; Özdemir, Samet; Pilevne, Şeniz Nur; Çelebi, Ali Rıza Cenk
The beta-adrenoceptor blocker timolol maleate (TML) is a commonly used pharmaceutical agent for the management of glaucoma. Conventional eye drops have limitations due to biological or pharmaceutical factors. Therefore, TML-loaded ethosomes have been designed to mitigate these restrictions and give a viable solution for reducing elevated intraocular pressure (IOP). The ethosomes were prepared using the thin film hydration method. Integrating the Box-Behnken experimental strategy, the optimal formulation was identified. The physicochemical characterization studies were performed on the optimal formulation. Then, in vitro release and ex vivo permeation studies were conducted. The irritation assessment was also carried out with Hen's Egg Test–Chorioallantoic Membrane model (HET-CAM), and in vivo evaluation of the IOP lowering effect was also performed on rats. The physicochemical characterization studies demonstrated that the components of the formulation were compatible with each other. The particle size, zeta potential, and encapsulation efficiency (EE%) were found as 88.23 ± 1.25 nm, -28.7 ± 2.03 mV, and 89.73 ± 0.42 %, respectively. The in vitro drug release mechanism was found as Korsmeyer-Peppas kinetics (R2=0.9923). The HET-CAM findings verified the formulation's eligibility for biological applications. The IOP measurements revealed no statistical difference (p>0.05) between the once-a-day application of the optimal formulation and the three-times-a-day application of the conventional eye drop. A similar pharmacological response was observed at lowered application frequencies. Therefore, it was concluded that the novel TML-loaded ethosomes could be a safe and efficient alternative for glaucoma treatment.
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.
Preparation and characterization studies of etodolac suppositories: investigation on oleaginous blends of Witepsol® H15
(Marmara University Press, 2023) Özdemir, Samet; Üner, Burcu; Karaküçük, Alptuğ
Etodolac is a non-steroidal anti-inflammatory drug that is categorized as a BCS class-II drug due to its low aqueous solubility and high permeability. Frequent dosing, extensive liver metabolism, and low dissolution rates are major limitations of etodolac. The present study focuses on the designing of novel suppository base blends for providing an effective delivery of etodolac. The oils (Caprylic/capric triglyceride, isopropyl isostearate, and isopropyl palmitate) were added to Witepsol® H15 to form suppository base blends. White, odorless, and torpedo-shaped suppositories were developed by using two parts of Witepsol® H15 and one part of the oil. All of the suppositories prepared with different blends were found uniform in weight and content. The mechanical strength of all suppositories was in an acceptable range for suppositories (2.0 – 3.8 kg/cm2). The suppositories showed a disintegration time between 13 and 19 minutes. First-order release kinetics were observed after the in vitro release studies. The suppository base blends released 85%- 90% of etodolac in the first hour while 60% of etodolac was released from Witepsol® H15 base alone. Prolonged drug release was achieved after 2 hours all of the formulations reached the plateau levels. The oil blends exhibited higher release percentages (96% - 99%) than plain Witepsol® H15 base (89%). Therefore novel suppository base blends could be a promising formulation ingredient for the etodolac suppositories.
Loteprednol loaded nanoformulations for corneal delivery by quality by design concepts: Optimization, characterization, and anti infammatory activity
(Springer, 2023) Üner, Burcu; Özdemir, Samet; Taş, Çetin; Üner, Melike; Özsoy, Yıldız
Loteprednol etabonate (LE) is a topical corticosteroid that uses inflammatory conditions of the eye. It has a low ocular bioavailability and side effects such as corneal disorder, eye discharge, and ocular discomfort. Therefore, it was decided to select the delivery systems, which are solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), and nanoemulsion (NE). Design of experiments (DoE) of SLN, NLC, and NE formulations were formulated by using the quality by design (QbD) approach. Precirol® ATO 5 and oleic acid were used as solid and liquid lipids, respectively, in SLN, NLC, and NE formulations. Physiochemical characterization was performed on the formulations. The optimized formulations' inflammatory effects have been appraised on human corneal epithelial cells employing the ELISA test. Physicochemical characterization studies and inflammatory effects were appraised. The sizes of optimized formulations of SLN, NLC, and NE were 86.19 nm, 82.38 nm, and 126.35 nm, respectively, with minimum polydispersity. The release behavior of the formulations is composed of both diffusion and erosion. ELISA test results proved that the formulations significantly reduced IL-1 and IL-6 levels (p < 0.05). D-optimal mixture experimental design allowed us to develop the most precise formulations of SLN, NLC, and NE. Furthermore, the optimized formulations could be promising candidates for treating an inflammation-based corneal disease of the eye.
Combination of St. John’s wort oil and neem oil in pharmaceuticals: An effective treatment option for pressure ulcers in intensive care units
(MPDI, 2023) Özdemir, Samet; Bostanabad, Saber Yari; Parmaksız, Ayhan; Canatan, Halil Can
Background and Objectives: Phytotherapeutically, various herbal remedies, such as St. John’s wort oil, have been introduced as wound care options. Recently, Neem oil has been considered a herbal option for the management of superficial wounds. Wound care is a complex process that involves several factors including the patient, caregiver, and medications. Herbal combinations could be an alternative to the chemical counterparts in the wound care area. This report includes an investigation of the possible supportive impacts of the St. John’s wort and Neem oil containing ointment (W Cura G Plus ®) in the management of pressure ulcers (PUs) in three intensive care unit (ICU) patients. Materials and Methods: The ointment was administered to individuals once daily for 42 consecutive days. The status of individuals was macroscopically monitored by measuring the PU area and histopathological assessment of the tissue sections taken on the first and last days of wound treatment. Results: The outcomes of the macroscopic and histopathological techniques exhibited that St. John’s wort and Neem oil containing ointment provided a remarkable supportive impact on the patients that suffered from PUs in the ICUs. Conclusions: The combination of St. John’s wort and Neem oil could be suggested as an efficient active phytoconstituent for the management of PUs. The herbal ointments may be suggested as an alternative for the patients that have PUs in the ICUs.
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.
The role of extracellular vesicles in immunomodulation and pathogenesis of Leishmania and other protozoan infections
(IntechOpen, 2022) İşlek, Zeynep; Bozkurt, Batuhan Turhan; Üçışık, Mehmet Hikmet; Şahin, Fikrettin; Paul, Manash K.
Extracellular vesicles (EVs) have lately emerged as crucial mediators in parasite infections. Recent research suggests that protozoan parasites, including Leishmania, employ EVs as transport vehicles to deliver biologically active effector molecules such as parasitic virulence factors to modulate the host immune system and their microenvironment. The immunomodulatory effects of EVs play an essential role in the formation and progression of parasitic diseases. The immunomodulatory strategies applied by EVs of protozoan origin have similarities to the development and progression of other infections or diseases such as cancer. In this chapter, we will provide recent insights into the role of EVs in host-pathogen interactions, intercellularcommunication, immunomodulation and pathogenesis of Leishmania and other protozoan parasites, including Plasmodium spp., Toxoplasma spp. and Trypanosoma spp. In addition, biologically inspired by the immunomodulation strategies of protozoan parasites, new immunotherapeutic models are being currently investigated to implement EVs more intensively in both therapy and diagnostics. Therefore, besides highlighting the role of EVs in protozoan infections, this chapter sheds light briefly on new immunotherapeutic approaches utilizing the strategies of protozoan EVs in medicine.
Delivery of curcumin within emulsome nanoparticles enhances the anti‑cancer activity in androgen‑dependent prostate cancer cell
(SpringerLink, 2023) Bolat, Zeynep Büşra; İşlek, Zeynep; Şahin, Fikrettin; Üçışık, Mehmet Hikmet
Background Curcumin, a dietary polyphenol isolated from turmeric, is a potent phytochemical possessing intrinsic anticancer activities against various cancer types including prostate cancer. However, low water solubility and bioavailability of the compound are major challenges against its medical use. The objective of this study is to evaluate the therapeutic potential of curcumin-loaded emulsome nanoparticular system, i.e. CurcuEmulsomes, for the treatment of androgen dependent LNCaP prostate cancer cell line. Methods and results The antiproliferative efect of both free curcumin and CurcuEmulsome were investigated comparatively on LNCaP and PNT1A cells. Cell viability data indicates that the inhibition in proliferation of LNCaP cells becomes more efective when curcumin is provided with its emulsome formulation rather than its free form. Corresponding to a therapeutic index of 2.25, Half maximal inhibitory (IC50) and cytotoxic (CC50) concentrations of CurcuEmulsomes for LNCaP and PNT1A cells were estimated as 17.1 µM and 38.6 µM, respectively. The fuorescence signal of autofuorescence curcumin was preserved within the CurcuEmulsomes at 72 h after the treatment. Thus, CurcuEmulsomes prolonged biological activity of curcumin. Induced apoptotic cell death and stimulated cell cycle arrest at G2/M phase were attributed to antiproliferative activity of CurcuEmulsomes. Treatment of LNCaP cells with CurcuEmulsomes increased expression of caspase-3 signifcantly by 11.76-fold, whereas decreased cyclin D1, Bcl-2 and AR expression levels signifcantly by of 0.18, 0.06 and 0.46-fold, respectively. Conclusions Presented safety and anticancer activity of CurcuEmulsomes on LNCaP cell line highlights the potential of CurcuEmulsomes to beneft intrinsic anticancer activities of curcumin in androgen dependent prostate cancer therapy
Preparation and characterization studies of dorzolamide loaded ophthalmic implants for the treatment of glaucoma
(Turkish Pharmacists Association, 2023) Özdemir, Samet; Çakırlı, Egemen; Sürücü, Bilge; Aygüler, Cemre İrem; Üner, Burcu; Çelebi, Ali Rıza Cenk
Objectives: This study aimed to construct dorzolamide loaded ophthalmic implants for extended drug delivery and increased drug retention. Materials and Methods: Carboxymethyl cellulose and Chitosan were used to formulate the ophthalmic implants. The implants were prepared by solvent casting technique in existence of polyethylene glycol 6000 as plasticizer. Physiochemical characterization studies including mechanical characteristics (tensile strength, elongation at break, and Young’s modulus), bioadhesion studies, in vitro and ex vivo drug release studies were conducted. Results: Tensile strength of drug loaded ophthalmic implants were 10.70 and 11.68 MPa respectively. Elongation at break of Carboxymethyl cellulose and Chitosan implants were 62.00% and 59.05% respectively. The in vitro release profiles fit into the Higuchi type kinetic model. Ex vivo release study results for both implants were correlated with in vitro release investigations. Conclusion: Carboxymethyl cellulose and Chitosan based implants provide extended drug delivery. Implants were prepared by using carboxymethyl cellulose provide significantly slower in vitro release rate, and the drug retention on ocular surfaces has been increased. Thus, it has been concluded that, dorzolamide loaded carboxymethyl cellulose implants could provide effective treatment for glaucoma
Bir farmasötik ajan olarak kara mürver
(Nobel Bilimsel Eserler, 2022) Özdemir, Samet
Bitkiler geçmişten günümüze kadar pek çok hastalığın önlenmesi ve tedavi edilmesi amacıyla kullanılmaktadır. Son yıllarda bitkisel kaynaklı gıdalardaki aktif bileşenlerle ilgili araştırmalarda bir artış görülmektedir. Etnobotanik açıdan bakıldığında, dünya genelinde sıklıkla kullanılan bitkilerden biri de kara mürverdir (Sambucus nigra L.). Kara mürver, Avrupa, Asya, Kuzey Afrika ve Amerika’nın çoğu yerinde güneş ışığına maruz kalan yerlerde yetişen ve yaprak döken çalı şeklinde bir bitkidir. Yaz mevsimi başında çiçek açan kara mürver, 6 m yüksekliğe kadar ulaşabilir. Beyaz renkli ve küçük hermafrodit çiçekleri olan kara mürverin yaz sonunda koyu mor renkli meyveleri gözlemlenebilir.
Development of monolithic matrix type transdermal patches containing cinnarizine: physical characterization and permeation studies
(Universidade de São Paulo, 2022) Damgalı, Şükran; Özdemir, Samet; Kaya, Gizem; Barla Demirkoz, Aslı; Üner, Melike
To overcome the problems associated with bioavailability and systemic side effects of the drug by oral administration, monolithic matrix type transdermal patches containing cinnarizine (CNZ) were developed. For this purpose, films based on hydroxypropyl methylcellulose and polyvinylpyrrolidone as matrix-forming polymers were designed. Physical characteristics of transdermal films and drug-excipient compatibility were investigated. Factors affecting in vitro drug release and ex vivo skin penetration and permeation of the drug were studied. It was confirmed that films displayed sufficient flexibility and mechanical strength for application onto the skin for a long time period. Ex vivo penetration experiments gave satisfactory results for transdermal drug delivery through rat skin. The parameters determining good skin penetration were also evaluated. The highest drug permeation rate was obtained with incorporation of Transcutol® (0.102 mg/cm2/h) into the base CNZ formulation, followed by propylene glycol (0.063 mg/cm2/h), menthol (0.045 mg/cm2/h), and glycerin (0.021 mg/cm2/h) as penetration enhancers (p < 0.05). As a result, the developed transdermal patches of CNZ may introduce an alternative treatment for various conditions and diseases such as idiopathic urticarial vasculitis, Ménière’s disease, motion sickness, nausea, and vertigo. Thus, the risk of systemic side effects caused by the drug can be reduced or eliminated.
Development of lipid nanoparticles for transdermal loteprednol etabonate delivery
(Taylor and Francis, 2022) Üner, Burcu; Özdemir, Samet; Taş, Çetin; Özsoy, Yıldız; Üner, Melike
Aim Loteprednol etabonate (LE) is a new generation corticosteroid that is used for the treatment of inflammatory and allergic conditions of the eye. Therefore, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) were attempted to improve for transdermal LE delivery for the first time. Methods SLN and NLC were produced by hot homogenization and ultrasonication technique. Their physical stability was monitored for 3 months of storage. Drug release and permeation of SLN and NLC through the porcine skin were investigated. Results It was determined that SLN and NLC mean particle size as 139.1 nm had a homogeneous particle size distribution (∼0,169 PI) and mean charge as -23.6. They were found to be stable both physically and chemically at room temperature. Conclusion SLN and NLC formulations of LE can be stated among the systems that can be an alternative to conventional systems with less side-effect in the treatment of inflammatory problems.
Antileishmanial activity of BNIPDaoct- and BNIPDanon-loaded emulsomes on leishmania infantum parasites
(Frontiers Media S.A., 2022) İşlek, Zeynep; Üçışık, Mehmet Hikmet; Keskin, Elif; Onur Sucu, Bilgesu; Gomes-Alves, Ana G.; Tomás, Ana M.; Güzel, Mustafa; Şahin, Fikrettin
Among bisnaphthalimidopropyl (BNIP) derivatives, BNIPDaoct and BNIPDanon recently came forward with antileishmanial activities beyond the standard, commercialized antileishmanial therapies. However, high-level toxicity on macrophages plus poor aqueous solubility and poor bioavailability of the compounds limit their application in therapies. Addressing these limitations, the present study introduces BNIPDaoct- and BNIPDanon-loaded emulsomes as lipid-based nanocarrier systems. Accordingly, emulsome formulations were prepared with the presence of BNIP compounds. The average diameters of BNIPDaoct- and BNIPDanon-loaded emulsomes were found as 363.1 and 337.4 nm, respectively; while empty emulsomes differed with a smaller average particle diameter, i.e., 239.1 nm. All formulations exhibited a negative zeta potential value. The formulations achieved the encapsulation of BNIPDaoct and BNIPDanon at approximately 0.31 mg/ml (501 µM) and 0.24 mg/ml (387 µM), respectively. The delivery of BNIP within the emulsomes improved the antileishmanial activity of the compounds. BNIPDaoct-loaded emulsome with 50% inhibitory concentration (IC50) value of 0.59 ± 0.08 µM was in particular effective against Leishmania infantum promastigotes compared to free BNIPDaoct (0.84 ± 0.09 µM), free BNIPDanon (1.85 ± 0.01 µM), and BNIPDanon-loaded emulsome (1.73 ± 0.02 µM). Indicated by at least ≥ 2-fold higher 50% cytotoxic concentration (CC50) values, the incorporation of BNIP into emulsomes significantly reduced the toxicity of BNIPs against macrophages, corresponding to up to 16-fold improvement in selectivity index (CC50/IC50) for L. infantum promastigotes. The infection rates of macrophages were determined using dual-fluorescent flow cytometry as 68.6%. Both BNIP formulations at concentration of 1.87 µM reduced the parasitic load nearly to 40%, whereas BNIPDaoct-loaded emulosmes could further decrease the parasitic load below 20% at 7.5 µM and above. In conclusion, the incorporation of BNIPDaoct and BNIPDanon into emulsomes results in water-soluble dispersed emulsome formulations that do not only successfully facilitate the delivery of BNIP compounds into the parasites and the Leishmania-infected macrophages in vitro but also enhance antileishmanial efficacy as proven by the decline in IC50 values. The selectivity of the formulation for L. infantum parasites further contributes to the challenging safety profile of the compounds. The promising in vitro antileishmanial efficacy of BNIP-loaded emulsomes highlights the potential of the system for the future in vivo studies.

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