Farmasötik Teknoloji Ana Bilim Dalı Koleksiyonu

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

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Tannic acid and copper-modified ZIF-8 metal organic framework as a cefotaxime delivery system for antimicrobial activity
(Galenos Publishing House, 2026) Pirinççi Tok, Yağmur; Özsoy, Münteha; Damar Çelik, Damla
Objectives: Antibiotic resistance has become a global public health threat. Cefotaxime (CTX), a third-generation cephalosporin, is approved for use in infants, children, and adults with various microbial infections, particularly those affecting the central nervous system. This study aimed to synthesize and characterize zeolitic imidazolate framework (ZIF)-8-based drug delivery systems (DDSs) to enhance antimicrobial activity and control CTX release. Materials and Methods: ZIF-8 was synthesized via the coordination network of Zn ions and 2-methylimidazole and subsequently modified with tannic acid (TA) and copper ions (Cu2+). ZIF-8 MOF and its derivatives were characterized by Fourier Transform Infrared, zeta potential, in vitro dissolution rate, and in vitro antimicrobial activity. Results: The drug loading capacity and encapsulation efficiency were found to be 39.50 ± 1.19% and 98.75 ± 2.96%, respectively, for ZIF-8@TA@CTX, and 40.75 ± 1.22% and 97.75 ± 2.93%, respectively, for ZIF-8@TA@Cu@CTX. Following 48 hours, the drug released from ZIF-8@TA@Cu@CTX was detected at 62.83 ± 1.89% at pH 5.0 and 83.19 ± 2.50% at pH 7.4 after 48 h, with dissolution profiles best fitting the Korsmeyer–Peppas model. The synthesized DDSs demonstrated a higher antibacterial activity against gram-positive bacteria than against gram-negative bacteria. Conclusion: ZIF-8 MOF DDs may serve as an alternative for delivering drugs to infected areas due to their controlled release under low pH conditions.
A dual-drug nanocarrier strategy for ocular fungal infections: Micelles embedded in electrospun nanofibers
(MDPI Publishing, 2026) Uzel, Egemen; Durgun, Meltem Ezgi; Aydilek, Neriman; Hacıoğlu, Mayram; Güngör, Sevgi; Özsoy, Yıldız
Ocular fungal diseases are associated with severe infection and pain and, in advanced stages, can lead to vision loss. Current treatment options are limited to the topical ap plication of conventional drugs, and the bioavailability of these drugs is quite limited due to ocular barriers. In this study, a dual-drug nanodelivery system was developed to improve intraocular drug delivery by combining antifungal and anti-inflammatory therapies. Posaconazole (PSC), a broad-spectrum triazole antifungal agent, and dexke toprofen trometamol (DKP), a rapidly acting nonsteroidal anti-inflammatory drug, were co-loaded onto polymeric micelles and then incorporated into electrospun poly(vinyl alco hol)/poly(vinylpyrrolidone) (PVA/PVP) nanofiber intraocular implants. DSC, XRD, FTIR, and FESEM analyses showed that both APIs were successfully converted into nanofiber form without disrupting the micelle structure. Comparative studies with DKP solution and PSC commercial oral suspension (Noxafil® 40 mg/mL) showed that the produced micelle loaded nanofibers provided sustained release and significantly increased ex vivo ocular permeation and penetration. In vitro antifungal activity tests demonstrated efficacy against Candida albicans, and HET-CAM toxicity tests showed that the micelle-loaded nanofibers were non-irritating and suitable for ocular application. Overall, the micelle-loaded electro spun nanofiber ocular inserts developed in this study represent a promising platform for combined antifungal and anti-inflammatory ocular therapy.
Thermoresponsive sol–gel system incorporating oleuropein-rich olive leaf extract for enhanced wound healing and antibiofilm activity
(MDPI Publishing, 2026) Alparslan, Levent; Özdemir, Samet; Karacan, Burak; Torkay, Gülşah; Bal Öztürk, Ayça; Tutar, Ömer Faruk; Özcan Bülbül, Ece; Sardaş, Semra; Kala, Zübeyde Merve; Özalp, Yıldız
Oleuropein, the principal secoiridoid phenolic compound of olive leaves (Olea europaea L.), is recognized for its broad-spectrum antimicrobial, antibiofilm, antioxidant, and tissue regenerative properties. However, its effective local therapeutic application remains chal lenging due to rapid clearance from the site of administration and limited residence time. In this study, an oleuropein-rich aqueous olive leaf extract was incorporated into a ther moresponsive sol–gel delivery system designed for localized application. The formulation was engineered to remain in a low-viscosity sol state at room temperature and to undergo a temperature-triggered sol-to-gel transition near physiological temperature (~33 ◦C), en abling in situ gel formation. Oleuropein content was quantified using a validated HPLC method, and the formulation was characterized with respect to physicochemical parame ters, thermoreversible gelation behavior, particle size distribution, mechanical properties, and spreadability. Biological performance was evaluated through in vitro cytocompati bility (MTT assay), fibroblast migration (scratch assay), and collagen deposition (Sirius Red staining) in L929 fibroblasts, as well as antibiofilm activity against representative Gram-positive and Gram-negative bacterial strains. The developed sol–gel system demon strated stable physicochemical characteristics, rapid and reversible thermogelation, suitable mechanical and spreading properties, concentration-dependent inhibition of biofilm for mation, and acceptable cytocompatibility within the tested concentration range. Notably, the formulation supported fibroblast viability and collagen-associated responses at opti mized concentrations. Overall, the results indicate that the proposed thermoresponsive sol–gel formulation represents a promising strategy for the localized delivery of oleuropein rich olive leaf extract, combining physicochemical stability with dual wound-healing and antibiofilm functionality.
Evaluation of the wound healing potential of volatile oil-loaded nanofibers
(Thieme, 2026) Kuruldak, Ebru; Durgun Kılıç, Meltem Ezgi; Olcay, F. N.; Aydın, M.; Aydilek, N.; Çelik, Y. S.; Gülsoy Toplan, G.
Volatile oils possess antimicrobial and anti-inflammatory activities beneficial for wound healing. In time, nanotechnological approaches like nanofibers have been developed to enhance volatile oils’ stability, bioavailability and controlled release [1] Our study aims to develop nanofibers loaded with a mixture of volatile oils to utilize in wound healing. A volatile oil mixture was prepared according to the book of Demirezer et al. [2]. Four volatile oils were used namely; pelargonium, chamomile, immortelle and tea tree oils were used as volatile oils to prepare the mixture. Polyvinylpyrrolidone (PVP) 360 was used for volatile oil-loaded nanofiber production. Formulations with polymer concentration of 15% (w/v) and 1 ml of volatile oil mixture were electrospun. The experimental setup varied in voltage, flow rate and collector distance. GC-MS analyzes of the mixture of oil and nanofibers were conducted. While the microbroth dilution method was applied to both volatile oil and the mixture oil, disc diffusion method used for the nanofiber parts. Strains were Staphylococcus aureus ATCC 29213, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Candida albicans ATCC 10231 [3] [4]. The results of antimicrobial tests are given in Table 1. The nanofibers collected in the collector formed a circle shape with a diameter of 5 cm in the production where a homogeneous fiber throw occurred. Only 4-terpinol, neryl acetate, geraniol and citronellol are found in GC-MS results of nanofibers. When all results were evaluated jointly, mixture volatile oil loaded nanofibers can be promising for wound healing activity however additional experiments should be designed by changing the parameters.
A quality by design study of the use of microfluidic nanoprecipitation for the generation of sub-100 nm drug nanocrystals
(Elsevier, 2026) Pirinçci Tok, Yağmur; Abukhamees, Shorooq; Fitaihi, Rawan; Demiralp, Burcu; Özsoy, Yıldız; Craig, Duncan
Although drug nanocrystals have attracted considerable interest within the pharmaceutical industry, there remain issues with the production of nanocrystals with a size below 100 nm. The aim of the present study is to develop a stable, reproducible Canagliflozin (CFZ) sub-100 nm nanosuspension system using microfluidic nanoprecipitation and Quality by Design (QbD) techniques. By means of the circumscribed central composite design (CCCD), critical parameters of the microfluidic nanoprecipitation process and nanosuspension formula tion components were optimised. Optimal CFZ nanosuspension with Z-average of 89.52 ± 3.30 nm, PDI of 0.12 ± 0.01 and drug content of 92.49 ± 0.03 % was successfully fabricated using Soluplus as a stabiliser. An increase in saturation solubility corresponding to approximately 250 times the value of the pure CFZ in water was noted. The optimised CFZ nanosuspension was solidified by freeze-drying and electrospraying. Overall, the study has demonstrated that by using a combination of microfluidics and QbD it is promising to generate stable sub-100 nm nanocrystals with high yield, and narrow size distribution and favourable stability.
Preparation and in vitro characterisation of nanofibers for enhancing the water solubility of poorly soluble drugs
(İstanbul University Press, 2025) Karamürsel, Elif; Uzel, Egemen; Aydilek, Neriman; Durgun, Meltem Ezgi; Özsoy, Yıldız
Background and Aims: As the drug discoveries of the modern century have led to a rapid increase in the number of new drug candidates with low water solubility, nanofiber drug delivery systems have become a promising technology to increase the water solubility of drugs with a high surface-to-volume ratio. In this study, we aimed to prepare a nanofiber of a molecule with low water solubility and investigate its changing solubility properties. Methods: Three nanofiber dosage forms containing olanzapine (OLZ) active substance were developed by the electrospinning method using polyvinyl alcohol (PVA) polymer. Drug loading efficiency, zeta potential determination, electrical conductivity, rheology, field emission scanning electron microscopy (FESEM), Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) analyses were performed to evaluate the in vitro characterisation of the formulations. The solubility profile of the optimised formulations in pH 7.4 phosphate buffer was evaluated. The stability of optimised formulations was evaluated in terms of physical properties (colour, shape, weight, diameter, and thickness) and drug amount for 35 days. Results: It was determined that the electrospinning property of the nanofiber preparation solution increased with the addition of ethanol to the polymer solvent medium. The active substance distribution in the nanofiber layer was more homogeneous in the N78 and N79 coded formulations with high zeta potential values compared to N69. Contrary to the homogeneous distribution problem, the loading efficiency of the N69-coded formulation containing chloroform (~29%) was higher than that of N79 (~9.8%). A 24-h solubility study in pH 7.4 phosphate buffer of the N78-coded formulation, which has an active ingredient loading efficiency of ~80.4%, confirmed the increased solubility of OLZ in water in the nanofiber drug delivery system. Conclusion: Further studies are needed to convert these model formulations into final drug products.
Formulation and characterization of an oleuropein-enriched oral spray gel: Microbiological performance and in ovo histopathological safety
(MDPI Publishing, 2026) Alparslan, Levent; Özdemir, Samet; Karacan, Burak; Tutar, Ömer Faruk; Doğan, Tunay; Akar, Remzi Okan; Yıldırım, Elifnur Gizem; Erdoğan, Nusret
Background/Objectives: Oleuropein is a bioactive phenolic compound from olive leaves with antimicrobial and antioxidant activity. This study aimed to develop a sprayable oral gel containing an oleuropein-rich aqueous extract and to evaluate its pharmaceutical performance antimicrobial efficacy and in ovo biological response. Methods: Oleuropein content was quantified using a validated chromatographic method. Polymeric systems were screened to select an optimized sprayable formulation. Physicochemical stability, dose uni formity, and antimicrobial activity against major cariogenic bacteria were evaluated. In ovo biological evaluation was conducted using the chick chorioallantoic membrane angiogene sis model together with histopathological examination of embryonic heart and liver tissues. Results: Oleuropein content was determined as 288.6 µg/mL in the olive leaf extract and 255.1 µg/mL in the final formulation. The optimized oral spray showed stable physico chemical properties, with pH maintained at 6.90 ± 0.02 and no relevant changes in viscosity during storage. The mean delivered dose per actuation was 0.128 ± 0.015 g, corresponding to 32.6 µg oleuropein per spray. The formulation exhibited inhibitory activity against all tested cariogenic microorganisms, with MIC values ranging from 13.3 to 170.7 µg/mL and MBC values generally two-fold higher. In the CAM assay, significant concentration- and time-dependent antiangiogenic effects were observed after 24–48 h at moderate and higher concentrations. Histopathological evaluation revealed dose-dependent acute degenerative and congestive changes in heart and liver tissues without evidence of fibrosis or steatosis. Conclusions: The oleuropein-based sprayable oral gel is a promising localized delivery system with adequate stability dose uniformity and antimicrobial efficacy. In ovo findings provide a conservative assessment of systemic exposure and support further development for oral biofilm and caries-related applications.
Development of brimonidine-loaded ethosomes for glaucoma: Investigation of intraocular pressure-lowering potential in vivo
(MDPI Publishing, 2026) Özdemir, Samet; Sağıroğlu, Ali Asram; Şen, Eslim; Gelmez Yıldız, Büşra; Karimli, Laman; Durgun, Meltem Ezgi; Çelebi, Ali Riza Cenk; Özsoy, Yıldız
Background/Objectives: Brimonidine tartrate (BRT), a selective α2-adrenergic receptor agonist, is commonly used in the treatment of glaucoma. However, conventional eye drop formulations suffer from poor ocular bioavailability and rapid elimination. This study aimed to develop and evaluate BRT-loaded ethosomes as a nanocarrier-based alternative to enhance intraocular delivery and therapeutic efficacy. Methods: Ethosomes were prepared using the thin-film hydration method and optimized via central composite design. The optimized formulation was subjected to physicochemical characterization, in vitro release testing, and ocular irritation assessment using the Hen egg test—chorioallantoic membrane (HET-CAM) model. Additionally, the intraocular pressure (IOP)-lowering efficacy of the formulation was evaluated in a rat glaucoma model. Results: The optimized ethosomal formulation exhibited favorable physicochemical properties, including a mean particle size of 122.6 ± 0.7 nm, zeta potential of −1.8 ± 0.9 mV, and encapsulation efficiency of 87.33 ± 0.04%. In vitro release data followed Higuchi kinetics. HET-CAM analysis indicated non-irritancy. In vivo, the ethosomal BRT formulation achieved comparable IOP-lowering effects to the marketed eye drops at one-third of the dose. Conclusions: The developed BRT loaded ethosomal system demonstrated promising physicochemical stability, sustained release, and therapeutic potential. These findings suggest that ethosomes may offer a safe and effective strategy for enhancing the ocular delivery of BRT in glaucoma therapy.
Influence of drying methods on redispersibility and dissolution of canagliflozin nanocrystals: A comparative approach
(MDPI Publishing, 2026) Pirinçci Tok, Yağmur; Demiralp, Burcu; Güngör, Sevgi; Sarıkaya, Ali Osman; Aldeniz, Emre Erol; Dude, Udaya Kumar; Özsoy, Yıldız
Background/Objectives: Canagliflozin (CFZ) is the first sodium glucose co-transporter 2 (SGLT-2) inhibitor and is characterized by poor water solubility and permeability, resulting in low oral bioavailability. In this study, a CFZ nanosuspension (CFZ-NS) was converted into a solid form to improve the physical stability of CFZ nanocrystals (CFZ-NCs) and to enable formulation as a tablet dosage form. Methods: To achieve adequate redispersibility of dried CFZ-NCs, fluid bed granulation and spray-drying methods were employed, and the effects of critical process parameters were investigated. The stability of spray dried nanocrystal tablets (NCs-SD-TAB) was evaluated over a three-month period under storage conditions of 25 ± 2 ◦C with 60 ± 5% relative humidity (RH) and 40 ± 2 ◦C with 75 ± 5% RH. Results: The highest redispersibility index (94%) was obtained using the spray-drying method. Tablets prepared with spray-dried NCs-SD-TAB exhibited a significantly higher in vitro dissolution rate under non-sink conditions compared with control tablets prepared using unprocessed CFZ with the same excipients, as well as the marketed product. NCs-SD-TAB showed an approximately three-fold increase in drug release at 15 min in 0.1 N HCl, with a pH 4.5 acetate buffer and pH 6.8 phosphate buffer, which simulate gastrointestinal pH conditions, relative to the marketed product. Conclusions: Overall, these results indicate that nanocrystal technology represents a promising approach for CFZ as an improved oral drug-delivery system, primarily due to its solubility enhancement capabilities.
Polyherbal ointment with bromelain for chronic diabetic wounds: Insights from a clinical case series
(Springer Nature Link, 2025) Bostanabad, Saber Yari; Özdemir, Samet; Saadati, Mahrokh; Karaca, Banu; Şener, Alper
Purpose Chronic diabetic wounds are characterized by prolonged inflammation and impaired healing. This study evaluates a novel polyherbal ointment, W Cura D Plus®, which contains Azadirachta indica oil, Hypericum perforatum oil, and bro melain from Ananas comosus. After initial debridement with W Cura D Plus®, treatment continued with W Cura G Plus®. To our knowledge, this is the first clinical report examining this specific combination in the treatment of chronic diabetic wounds. Methods A single-center clinical case series was conducted in 13 diabetic patients with Wagner grade 2–3 diabetic foot ulcers of at least 4 weeks’ duration. All patients were on standard type 2 diabetes therapy (oral agents and/or insulin) and routine wound care prior to enrollment. W Cura D Plus® was applied daily for 7 days to promote debridement, followed by W Cura G Plus® until complete closure or no further reduction in ulcer size for two consecutive weeks. Clinical endpoints included wound area, closure percentage, and recovery time. White blood cell (WBC) and C-reactive protein (CRP) levels were monitored. Results Fourteen wound observations were analyzed. Mean wound area decreased from 25.07±24.56 cm² at baseline to 7.38±5.15 cm² (p=0.0103), and mean closure rate was 64.15±0.23% (p=0.0108), surpassing the 50% benchmark for clini cally meaningful improvement. Recovery time averaged 97.7 days compared to baseline (initial status prior to treatment). WBC and CRP significantly declined (p<0.0001). No adverse events were reported. Conclusion This polyherbal formulation may represent a safe adjunct to standard care, but larger controlled trials are needed to confirm efficacy.
Smart thermoresponsive sol–gel formulation of polyhexanide for rapid and painless burn and wound management
(MDPI Publishing, 2025) Alparslan, Levent; Torkay, Gülşah; Bal Öztürk, Ayça; Köksal Karayıldırım, Çinel; Özdemir, Samet
Traditional wound and burn treatments often fall short in balancing antimicrobial efficacy, patient comfort, and ease of application. This study introduces a novel, transparent, ther moresponsive sol–gel formulation incorporating polyhexamethylene biguanide (PHMB) for advanced topical therapy. Utilizing Poloxamer 407 as a biocompatible carrier, the formulation remains a sprayable liquid at room temperature and instantly gels upon contact with body temperature, enabling painless, pressure-free application on sensitive, injured skin. Comprehensive in vitro and in vivo evaluations confirmed the formulation’s broad-spectrum antimicrobial efficacy (≥5 log10 reduction in 30 s), high biocompatibility (viability > 70% in fibroblasts), non-irritancy (OECD 425-compliant), and physical stabil ity across three months. Importantly, the formulation maintained fibroblast migration capacity—crucial for wound regeneration—while exhibiting rapid sol-to-gel transition at ~34 ◦C. These findings highlight the system’s potential as a next-generation wound dressing with enhanced user compliance, transparent monitoring capability, and rapid healing support, particularly in disaster or emergency scenarios.
Nanocrystal based approach in colon targeting
(Elsevier, 2025) Pirinçci Tok, Yağmur; Güngör, Sevgi; Özsoy, Yıldız
Nanocrystals have unique characteristics among of the drug delivery systems in nanosized through high drug loading, favorable effects on pharmacokinetics, reduced toxicity, and easy of scaling-up. Nanocrystals are basically active pharmaceutical ingredient particles in the nanometer range, which is described generally as nanosuspension since they are produced by surrounding a stabilizer and suspending in a dispersion media. They can be administered via oral, buccal, nasal, pulmonary, parenteral, and ocular routes with different formulation technologies or brain delivery of nanocrystals. In recent years, there has been increased interest in colon-targeting nanocrystals where chitosan-derived stabilizers, pH-sensitive and time-released approaches, coating, and encapsulation strategies are being preferred. In this chapter, the features of drug nanocrystals, the principles of their manufacturing methods as well as stabilization mechanism of nanocrystals, and stabilizer agents used for their production and stabilization of the nanosuspension are handled out and the strategies focus on colon-targeting of nanocrystals drug delivery will be summarized. © 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.
The lenalidomide derivative loaded and quercetin modified MIL-100 based novel drug delivery system for breast cancer treatment
(Editions de Sante, 2025) Özsoy, Münteha; Pirinçci Tok, Yağmur; Güney Eskiler, Gamze; Tok, Fatih; Karakuş, Sevgi; Özsoy, Yıldız; Özaçar, Mahmut
Lenalidomide (L0) is an immunomodulatory agent with a range of effects, including anticancer and anti-inflammatory activity, and is commonly utilized in treating multiple myeloma. A derivative of lenalidomide (L1) has been synthesized to enhance its effects and to target different cancer cell types. In this study, the lenalidomide derivative L1, with the chemical structure 1-[2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl]-3-(p-tolyl)urea, was loaded onto a novel drug delivery system (DDS), and its activity was assessed towards triple-negative breast cancer cell lines (TNBC). MIL-100, a subclass of metal-organic framework (MOF) structures, was synthesized via a microwave-assisted hydrothermal method. MIL-100 was modified with quercetin (QC) as a linker, and its drug loading capacity was optimized, achieving a 95.18 % encapsulation efficiency. Additionally, the antioxidant properties of QC contributed to enhancing the performance of the DDS. In vitro drug release studies of the final product, MIL-100@QC@L1, were successfully conducted. The cytotoxic influences of the formulation on MDA-MB-231 cells were assessed using the WST-1 assay. After treatment with 10 μg/mL of MIL-100@QC@L1 for 24 h, the cell viability decreased significantly to 47.8 %, showing superior results compared to treatments with L0 and L1 alone.
Nanodelivery approaches of phytoactives for skin cancers: Current and future perspectives
(Bentham Science Publishers, 2025) Algın Yapar, Evren; Özdemir, Merve Nur; 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.
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.
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.

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